Diastereoselective synthesis of aziridine esters via amino selanyl esters

Article abstract of DOI:10.1016/j.tet.2005.12.030

A synthesis of aziridine esters based on the cyclisation of amino selanyl esters induced by the selanyl group activation was developed with either the Meerwein salt or NBS. Two asymmetric approaches are proposed: the diastereoselective reductions of α-sel

Full text of DOI:10.1016/j.tet.2005.12.030

Tetrahedron 62 (2006) 2657–2670
Diastereoselective synthesis of aziridine esters
via amino selanyl esters
*
Catherine Miniejew, Francis Outurquin and Xavier Pannecoucke
*
´
`
Universite et INSA de Rouen-IRCOF, UMR 6014 CNRS, 1 rue Tesniere, 76821 Mont Saint Aignan, France
Received 3 November 2005; revised 8 December 2005; accepted 14 December 2005
Available online 18 January 2006
Abstract—A synthesis of aziridine esters based on the cyclisation of amino selanyl esters induced by the selanyl group activation was
developed with either the Meerwein salt or NBS. Two asymmetric approaches are proposed: the diastereoselective reductions of a-selanyl
b-iminoesters derived from a-oxoesters, which lead to cis chiral aziridine esters 6 and 60; and the diastereoselective conjugate additions of a
chiral amide to a,b-unsaturated esters providing trans chiral aziridine esters 6 and 600.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
intramolecular substitution is well documented.13 Our
laboratory is interested in selenium methodology, which has
provided useful synthetic tools for organic chemists.14
Previously reported work, bifunctional synthons such
as a-selanyl carbonyl derivatives have especially been
investigated.15 We developed specific methods to prepare
a-selanyl imines, which after reduction led to the correspond-
ingb-selanylaminesthatarepotentialprecursorsofaziridines.
We first promoted the cyclisation of b-selanyl amines using
Meerwein salt, which was subsequently improved using
N-bromosuccinimide (NBS).16,17 The synthesis of non-
functionalized aziridines from a-selanyl aldehydes and
a-selanyl ketones has recently been reported.17b
The aziridine moiety is present in a wide variety of natural
biologically active compounds like antitumor and antibiotic
agents.1 Synthetic aziridines exhibit multiple biological
properties, such as enzyme inhibitors2 and DNA alkylation
agents since their ring strain. They are, in particular,
susceptible for regio- and stereoselective ring opening.3
Thus, they are useful precursors for diverse nitrogen
containing compounds,4 notably chiral amino acids.5
Several reviews have surveyed the asymmetric synthesis of
aziridines.6 One pathway to obtain chiral aziridines consists
of the addition of nitrenoid compounds to alkenes,7 or of
carbenes to imines,8 in presence of asymmetric catalysts.
Nonetheless, the conceptually simplest approach relies on
the nucleophilic attack of a nitrogen atom on an adjacent
carbon atom bearing a leaving group.9 In this manner,
enantiomerically pure starting materials such as amino
acids, carbohydrates or hydroxy acids can be used and lead
to aziridines after displacement of the hydroxyl group
through a SN2 process.10 Similarly, aziridine synthesis by
derivation of a sulfonium group has been reported.11
We next focussed our attention on the preparation of chiral
aziridine esters. Indeed we had observed a syn diastereo-
selection during the reduction of imines derived from
b-selanyl a-oxoesters.16 Treatment of the syn configured
b-selanyl a-aminoesters by the Meerwein salt provided
corresponding cis aziridine esters. In continuation of this
work, herein we report a comparison between the Meerwein
salt and NBS activation of these substrates, and our attempt
to access chiral aziridine esters by introducing an additional
asymmetric centre on the amine group (path A, Scheme 1).
We also propose a new pathway that would provide
aziridine esters via b-amino a-selanylesters prepared from
a,b-unsaturated esters (path B, Scheme 1).
The selanyl group is known to be easily displaced under mild
conditions by nucleophiles when it has an activated IV
oxidation state, such as selenone or selenonium salt.12 Thus,
epoxides formation from b-hydroxy selenides through
Keywords: Selenium activation; Synthetic aziridines; Meerwein salt; N.
Bromosuccinimide.
2. Results and discussion
*
Corresponding authors. Tel.: C33 2 3552 2402; fax: C33 2 3553 2959;
e-mail addresses: francis.outurquin@univ-rouen.fr;
xavier.pannecoucke@insa-rouen.fr
b-Selanyl a-oxoesters 1 were first converted into N-benzyl
imines in presence of titanium tetrachloride (Scheme 2).
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.12.030

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C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
O
R
HNR
*
SePh
R1
R1
R1
R1
N
*
*
CO2Et
CO2Et
CO2Et
*
CO2Et
*
*
R1
CO2Et
SePh
SePh
Path A
HNR
Path B
Scheme 1.
Me
Bn
O
Bn
N
HNB
n
N
R1
R2
1) i
2) ii
iii or iv
R1
R2
R1
R2
R2
R1
+
CO2Et
CO2Et
CO2Et
CO2Et
SePh
SePh
SePh
1
2
3
2'
Scheme 2. (i) BnNH2 (4 equiv), TiCl4, Et2O, 20 8C, 4 h; (ii) NaBH3CN (0.5 equiv), AcOH, EtOH, 0 8C, 1 h; (iii) Me3OBF4 (2 equiv), CH2Cl2, 12 h then NaOH
aq 1 N; (iv) NBS (1.1 equiv), CH3CN, 5 min then Na2CO3.
Reduction to the amine was performed with sodium
cyanoborohydride as it had been shown that this reducing
agent limits the deselenenylation of the substrates.15a Only
one diastereomer was observed in the NMR for the
corresponding b-selanyl a-aminoesters 2. Methylation of
the selanyl group with the Meerwein salt and treatment with
base led to aziridine esters 3 in 48–61% yields (Table 1).
The characteristic aziridine coupling constant JH2–H3
allowed us to unambiguously assign the cis stereochemistry
of aziridines 3 (JH2–H3Z6.3–6.8 Hz).18 Considering that
the cyclisation proceeds through an SN2 mechanism
we deduced a syn configuration for the b-selanyl a-
aminoesters 2. However, with the hindered substrate 2f,
no aziridine was obtained after the Meerwein salt action.
Only a N-methylation reaction was observed yielding 20f.
This undesired reaction, due to the nature of the activator
and which also occurred during the cyclisation of hindered
b-selanyl amines derived from a-selanyl aldhehydes, can
be suppressed by the use of NBS. Indeed treatment of
compound 2f with this reagent provided the desired
aziridine 3f in 65% yield. In addition, the cyclisation
reactions are much faster with NBS than with the Meerwein
salt (5 min instead of 12 h) and the aziridine yields are
slightly higher.
In order to access chiral aziridine esters, an additional
asymmetric centre has been introduced by replacing the
benzylamine by the (R)-phenylethylamine ((R)-PEA).
The resulting imines 4 were formed as two diastereo-
mers in equal proportion. Due to their instability, it
Table 1. Synthetic yields of aziridine esters 3 via Scheme 2
Substrate
1/2 Yield (%)
Cyclisation of 2 products, yield (%)
No.
R1
R2
Via iii
Via iv
1a
1b
1c
1d
1e
1f
Me
Et
nPr
iPr
Bn
Me
H
H
H
H
H
Me
47
54
51
46
52
55
3a, 49
3b, 57
3c, 61
3d, 54
3e, 48
3a, 45
3b, 66
3c, 67
3d, 61
3e, 52
2fN-Me, 51
3f, 65
Ph
HN
Ph
R1
iii or iv
N
CO2Et
+
O
N
Ph
R1
CO2Et
SePh
R1
R1
i
ii
5
6
CO2Et
CO2Et
SePh
SePh
Ph
1
4
HN
Ph
R1
N
iii or iv
CO2Et
Ph
R1
CO2Et
SePh
5'
6'
N
Me
CO2Et
6"a
Scheme 3. (i) (R)-PEA (4 equiv), TiCl4, Et2O, 20 8C, 4 h; (ii) NaBH3CN (0.5 equiv), AcOH, EtOH, 0 8C, 1 h; (iii) Me3OBF4 (2 equiv), CH2Cl2, 12 h then
NaOH aq 1 N; (iv) NBS (1.1 equiv), CH3CN, 5 min then Na2CO3.

C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
Table 2. Synthetic yields of aziridine esters 6 and 60 via Scheme 3
2659
1/5-syn/50-syn
Yield (%), (5/50)
Cyclisation of 50 products, yield (%)
Substrate
No.
Cyclisation of 5 products, yield (%)
R1
Via iii
Via iv
Via iii
Via iv
600a, 57
6b, 55
6c, 61
6e, 48
60a, 49
60b, 56
60c, 52
60e, 44
60a, 51
60b, 49
60c, 58
60e, 52
1a
1b
1c
1e
Me
Et
nPr
Bn
47, (50/50)
53, (50/50)
51, (50/50)
50, (50/50)
6a, 47
6b, 50
6c, 55
6e, 41
Ph
N
Ph
CO2Et
HN
Ph
i
ii
CO2Et
CO2Et
H3C
H3C
H3C
SePh
7a
SePh
8a
SePh
9a
Scheme 4. (i) [(R)-BPEA (1.3 equiv), n-BuLi (1.3 equiv)], THF, K78 8C, 40 min; (ii) CAN (2.1 equiv), CH3CN/H2O, 20 8C, 1 h.
was not possible to separate them and these were
reduced as a crude mixture to provide b-selanyl
a-aminoesters 5 and 50 in equal proportion (Scheme 3,
Table 2).† Substrates 5 and 50 were separated by silica gel
chromatography and subjected to the cyclisation conditions.
Activation of the selanyl group of 5a and 50a (R1ZMe) by
the Meerwein salt led to the expected formation of cis
aziridine 6a and 60a, respectively. However, when 50a was
treated with NBS, 60a was obtained, but surprisingly trans
aziridine 600a was exclusively formed from 5a. This might
be explained by an enol equilibrium leading to the more
stable aziridine.19 Considering these results all the
cyclisation substrates were then subjected to both activators.
Nevertheless, only cis aziridine esters were obtained starting
from 5b–e and 50b–e no matter what the activation
conditions were. This confirmed the syn stereochemistry
of substrates 5 and 50. At this point of our study, we only
knew the relative stereochemistry of products 5, 50, 6 and 60
but could not attribute their absolute configuration.
favourable for the amide attack because of the minimisation
of steric interactions.22 The debenzylation with CAN is
selective and afforded amines 12 in 48–68% yields. After
deprotonation with LDA and addition of benzene selenienyl
bromide, b-amino a-selanylesters were obtained as two
diastereomers chromatographically separable 9 and 900 in
proportions ranging from 50/50 to 70/30 depending on
R1. The use of camphor selenienyl bromide23 as a chiral
electrophile did not increase the diastereoselectivity. The
cyclisation of substrates 900a–g by the Meerwein salt provided
trans aziridine esters 600a–g (JH2–H3Z2.7–2.8 Hz) which
implied an anti configuration for precursors 900. cis Aziridine
esters 6a–g (JH2–H3Z6.6–6.9 Hz) were observed from
treatment of compounds 9a–g with the same activator.
Similar results were obtained when the cyclisations were
carried out with NBS, except with three substrates. Indeed,
the activation with this reagent of the selanyl group of
compounds 9b (R1ZEt) led to a mixture of cis/trans
aziridines 6b/600b in a ratio 43/57 and compounds 9a,g
(R1ZMe, Ph) provided only the trans aziridines 600a,g. As
during the cyclisation of b-selanyl a-aminoesters 5a, these
partial or total C2 epimerisations occurred only when the
cyclisations were promoted by NBS and not by the Meerwein
salt. Considering that the configuration of one of the
stereogenic carbons was established by the diastereoselective
addition of the chiral amide, we were able to attribute the
absolute configuration of aziridines 6, 600 and with these
results in hand, we deduced the absolute configuration for
their precursors 9, 900 (Scheme 5, Table 3).
We thus developed another pathway to access similar
aziridine esters from a,b-unsaturated esters. Indeed, Davies
and co-workers have developed very efficient methods for
the diastereoselective conjugate additions of the lithium
amide derived from (R)-N-benzyl-N-phenylethylamine
((R)-BPEA).20 Initially addition of this chiral lithium
amide to the a-selanyl-a,b-unsaturated ester 7a gave an
unstable adduct 8a, which decomposed on silica gel or
alumina (Scheme 4). Thus 8a was used without any
purification in a debenzylation step with cerium ammonium
nitrite (CAN)21 to provide amine 9a as a single syn
diastereomer albeit in 28% yield over two steps, probably
due to a competitive retro-Michael reaction. Finally, the
selanyl group was introduced at the end of the reaction
sequence.
The fact, that cis aziridines 6 are the common product of
both pathways A and B (Scheme 1), allowed us to
distinguish between the two cis aziridines 6 and 60 obtained
previously from a-oxo esters 1 (path A) and, as a
consequence, to determine the absolute configuration of
b-selanyl a-aminoesters 5 and 50.
After addition of the chiral lithium amide on a,b-unsaturated
esters 10 only one diastereomer (R,R) was observed in the
NMR for products 11. Based on computational studies,
Davies and co-workers have shown that the Si face is the most
In conclusion, we have developed a synthesis of aziridine
esters based on the cyclisation of amino selanyl esters
induced by the selanyl group activation with either the
Meerwein salt or NBS. Two asymmetric approaches are
proposed: the diastereoselective reductions of a-selanyl
b-iminoesters derived from a-oxoesters, which lead to cis
† When R1ZiPr (1d), a complex mixture was obtained and no desired
amine could be isolated.

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C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
Ph
HN
R1
Ph
iv or v
N
CO2Et
R1
CO2Et
Ph
N
Ph
SePh
HN
R1
Ph
iii
i
ii
9
6
CO2Et
CO2Et
CO2Et
R1
+
R1
Ph
10
11
12
HN
R1
Ph
iv or v
N
CO2Et
R1
CO2Et
SePh
9''
6''
Scheme 5. (i) [(R)-BPEA (1.3 equiv), n-BuLi (1.3 equiv)], THF, K78 8C, 40 min; (ii) CAN (2.1 equiv), CH3CN/H2O, 20 8C, 1 h; (iii) LDA (2.1 equiv), THF,
K78 8C then PhSeBr (1.3 equiv), K78 8C, 20 min; (iv) Me3OBF4 (2 equiv), CH2Cl2, 12 h then NaOH aq 1 N; (v) NBS (1.1 equiv), CH3CN, 5 min then
Na2CO3.
Table 3. Synthetic yields of aziridines esters 6 and 600 via Scheme 5
12/9-syn/900-anti
Yield %, (9/900)
Cyclisation of 900
products, yield (%)
Substrate
10/11
Yield (%)
11/12
Yield (%)
Cyclisation of 9
products, yield (%)
No.
R1
Via iv
Via v
Via iv
Via v
600a, 58
600a, 53
600b, 47
600a, 59
600b, 51
10a
10b
Me
Et
79
75
68
66
65, (50/50)
59, (50/50)
6a, 51
6b, 53
6b/600b
(43/57), 48
6c, 61
600c, 50
600d, 48
600e, 39
600g, 52
600c, 51
600d, 53
600e, 48
600g, 55
10c
10d
10e
10g
nPr
iPr
Bn
Ph
72
82
78
89
63
53
62
48
56, (50/50)
58, (60/40)
61, (70/30)
57, (70/30)
6c, 47
6d, 44
6e, 42
6g, 49
6d, 49
6e, 53
600g, 55
chiral aziridine esters 6 and 60; and the diastereoselective
conjugate additions of a chiral amide to a,b-unsaturated
esters providing trans chiral aziridine esters 6 and 600.
The comparison of the aziridine esters obtained by these two
synthetic ways allowed the attribution of the absolute
configuration to all the synthesized compounds.
Reduction of b-(phenylselanyl)a-iminoesters. To the
a-(phenylselanyl)a-iminoester (5 mmol) in ethanol
(60 mL) at 0 8C, under argon, were added successively
sodium cyanoborohydride (314 mg, 5 mmol) and acetic
acid (300 mg, 5 mmol). The reaction mixture was stirred
for 1 h at 0 8C and quenched with water (70 mL). After
dichloromethane (100 mL) addition, the aqueous phase was
separated and washed with dichloromethane (2!80 mL).
The combined organic phases were dried over MgSO4 and
concentrated. The crude product was purified by silica gel
chromatography (cyclohexane/ether: 85:15).
3. Experimental
THF was distilled over sodium/benzophenone. Ether was
dried over sodium. 1H NMR (300 MHz) and 13C NMR
(75.4 MHz) spectrum were recorded on a Brucker DPX 300
instrument and carried out in CDCl3. Chemical shifts (d)
were quoted in ppm downfield from tetramethylsilane
(TMS). Elemental analyses were obtained on a Carlo-Erba
1106 analyser and Mass Spectra on a HP5890 (electronic
impact 70 eV) using GC–MS coupling with a Jeol AX 500.
3.1.1. syn-Ethyl 2-benzylamino-3-(phenylselanyl)-
1
butanoate 2a.16 Oil, yieldZ47%. H NMR d: 1.11 (t, 3H,
JZ7.1 Hz, OCH2CH3), 1.37 (d, 3H, JZ7.1 Hz, H-4), 2.19
(s, 1H, NH), 3.23 (d, 1H, JZ5.7 Hz, H-2), 3.53 (qd, 1H, JZ
5.7, 7.1 Hz, H-3), 3.59 (d, 1H, JZ13.2 Hz, CH2Ph), 3.85 (d,
1H, JZ13.2 Hz, CH2Ph), 3.86 (dq, 1H, JZ7.1, 10.8 Hz,
OCH2CH3), 3.98 (dq, 1H, JZ7.1, 10.8 Hz, OCH2CH3),
7.17–7.47 (m, 10H, Ph). 13C NMR d: 14.6 (OCH2CH3), 20.6
(C-4), 43.2 (C-3), 52.8 (CH2Ph), 61.3 (OCH2CH3), 65.7 (C-
2), 127.5, 128.1, 128.7, 128.8, 129.3, 129.4, 135.7, 140.2
(Ph), 173.6 (C-1).
3.1. Synthesis of a-(phenylselanyl)a-aminoesters 2
Preparation of b-(phenylselanyl)a-iminoesters. Titanium
chloride (708 mg, 3.75 mmol, 0.75 equiv) in heptane (2 mL)
was slowly added to a solution of b-(phenylselanyl)
a-oxoester (5 mmol, 1 equiv) and amine (20 mmol, 4 equiv)
in anhydrous ether (70 mL), under argon, at 0 8C. The mixture
was stirred 30 min at 0 8C and then 3 h at room temperature.
The titanium salts were filtered and rinced with ether. The
organic phase was dried over MgSO4 and concentrated to
afford the desired b-(phenylselanyl)a-iminoesters.
3.1.2. syn-Ethyl 2-benzylamino-3-(phenylselanyl)-
pentanoate 2b.16 Oil, yieldZ54%. 1H NMR d: 0.92 (t, 3H,
JZ7.3 Hz, H-5), 1.03 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.73 (m,
2H, H-4), 2.10 (s, 1H, NH), 3.31 (td, 1H, JZ3.9, 7.2 Hz,
H-3), 3.35 (d, 1H, JZ3.9 Hz, H-2), 3.62 (d, 1H, JZ13.3 Hz,
CH2Ph), 3.71 (dq, 1H, JZ7.2, 10.8 Hz, OCH2CH3), 3.90 (d,
1H, JZ13.3 Hz, CH2Ph), 3.92 (dq, 1H, JZ7.2, 10.8 Hz,

C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
2661
OCH2CH3), 7.15–7.45 (m, 10H, Ph). 13C NMR d: 13.1
(OCH2CH3), 14.4 (C-5), 27.5 (C-4), 52.8 (C-3), 52.9
(CH2Ph), 61.2 (OCH2CH3), 63.6 (C-2), 126.3, 126.9, 127.3,
127.4, 127.8, 128.8, 133.7, 140.4 (Ph), 173.6 (C-1).
solution of sodium hydroxide 1 N (10 mL). The aqueous
phase was extracted with dichloromethane (2!10 mL).
The combined organic phases were dried over MgSO4
and concentrated. The crude product was purified by silica
gel chromatography (cyclohexane/ether: 75:25) to afford
aziridine 3.
3.1.3. syn-Ethyl 2-benzylamino-3-(phenylselanyl)-
1
hexanoate 2c.16 Oil, yieldZ51%. H NMR d: 0.79 (t, 3H,
Procedure B with NBS. To the b-(phenylselanyl)
a-aminoester 2 (1 mmol) in acetonitrile (10 mL) was
added NBS (195 mg, 1.1 mmol) at room temperature.
After 5 min of stirring, the mixture became red-brown and
sodium bicarbonate (212 mg, 2 mmol) was introduced. The
mixture turned rapidly yellow. Water (10 mL) was added
and the aqueous phase was extracted with dichloromethane
(2!10 mL). The combined organic phases were dried over
MgSO4 and concentrated. The crude product was purified
by silica gel chromatography (cyclohexane/ether: 75:25) to
afford aziridine 3.
JZ7.3 Hz, H-6), 1.02 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.21–1.31 (m, 1H, H-5), 1.39–1.49 (m, 1H, H-5), 1.66–
1.70 (m, 2H, H-4), 2.26 (s, 1H, NH), 3.32 (d, 1H, JZ3.9 Hz,
H2), 3.39 (td, 1H, JZ3.9, 7.2 Hz, H-3), 3.57 (d, 1H, JZ
13.2 Hz, CH2Ph), 3.70 (dq, 1H, JZ7.2, 10.8 Hz,
OCH2CH3), 3.89 (d, 1H, JZ13.2 Hz, CH2Ph), 3.91 (dq,
1H, JZ7.2, 10.8 Hz, OCH2CH3), 7.11–7.45 (m, 10H, Ph).
13C NMR d: 12.7 (C-6), 13.0 (OCH2CH3), 20.1 (C-5), 35.1
(C-4), 49.3 (C-3), 51.4 (CH2Ph), 59.7 (OCH2CH3), 62.3 (C-
2), 126.0, 126.3, 127.2, 127.3, 127.8, 128.6, 133.7, 139.0
(Ph), 172.2 (C-1).
3.2.1. cis-Ethyl 1-benzyl-3-methylaziridine-2-carboxylate
3a.3j,16,18 Oil, yieldZ49% (A), yieldZ45% (B). 1H NMR d:
1.18 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.21 (d, 3H, JZ5.5 Hz,
CH3), 1.90–1.95 (m, 1H, H-3), 2.13 (d, 1H, JZ6.8 Hz, H-2),
3.54 (d, 1H, JZ13.9 Hz, CH2Ph), 3.61 (d, 1H, JZ13.9 Hz,
CH2Ph), 4.08 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3), 4.11 (dq,
3.1.4. syn-Ethyl 2-benzylamino-4-methyl-3-(phenyl-
selanyl)pentanoate 2d.16 Oil, yieldZ46%. 1H NMR d:
0.85 (d, 3H, JZ6.7 Hz, H-5), 0.96 (t, 3H, JZ7.3 Hz,
OCH2CH3), 1.09 (d, 3H, JZ6.7 Hz, H-5), 1.96–2.04 (m,
1H, H-4), 2.16 (s, 1H, NH), 3.17 (dd, 1H, JZ3.8, 7.4 Hz,
H-3), 3.50 (d, 1H, JZ3.8 Hz, H-2), 3.55 (d, 1H, JZ13.3 Hz,
CH2Ph), 3.61 (dq, 1H, JZ7.3, 10.7 Hz, OCH2CH3), 3.86
(dq, 1H, JZ7.2, 10.8 Hz, OCH2CH3), 3.87 (d, 1H, JZ
13.3 Hz, CH2Ph), 7.09–7.44 (m, 10H, Ph). 13C NMR d: 15.2
(OCH2CH3), 22.4 (C-5), 23.0 (C-5), 33.2 (C-4), 53.7
(CH2Ph), 61.1 (C-3), 61.9 (OCH2CH3), 64.2 (C-2), 128.2,
128.3, 129.5, 129.7, 130.1, 133.3, 135.4, 141.3 (Ph), 174.7
(C-1).
1H, JZ7.2, 10.7 Hz, OCH2CH3), 7.13–7.28 (m, 5H, Ph). 13
C
NMR d: 13.5 (CH3), 14.7 (OCH2CH3), 42.1 (C-3), 43.1 (C-2),
61.3 (OCH2CH3), 64.0 (CH2Ph), 127.5, 128.1, 128.6, 138.4
(Ph), 170.0 (C]O).
3.2.2. cis-Ethyl 1-benzyl-3-ethylaziridine-2-carboxylate
1
3b.16 Oil, yieldZ57% (A), yieldZ66% (B). H NMR d:
0.82 (t, 3H, JZ7.4 Hz, CH2CH3), 1.20 (t, 3H, JZ7.1 Hz,
OCH2CH3), 1.42–1.49 (m, 1H, CH2CH3), 1.56–1.63 (m,
1H, CH2CH3), 1.81 (q, 1H, JZ6.8 Hz, H-3), 2.17 (d, 1H,
JZ6.8 Hz, H-2), 3.52 (s, 2H, CH2Ph), 4.13 (q, 2H, JZ
7.2 Hz, OCH2CH3), 7.16–7.28 (m, 5H, Ph). 13C NMR d:
11.9 (CH2CH3), 14.7 (OCH2CH3), 21.5 (CH2CH3), 43.0 (C-
2), 48.5 (C-3), 61.3 (OCH2CH3), 64.3 (CH2Ph), 127.6,
128.5, 128.7, 138.4 (Ph), 170.2 (C]O). Anal. Calcd for
C14H19NO2: C, 72.07; H, 8.21; N, 6.00. Found: C, 72.38; H,
8.55; N, 6.19.
3.1.5. syn-Ethyl 2-benzylamino-4-phenyl-3-(phenyl-
1
selanyl)butanoate 2e.5b,16 Oil, yieldZ52%. H NMR d:
1.00 (t, 3H, JZ7.2 Hz, OCH2CH3), 2.21 (s, 1H, NH), 3.10
(dd, 1H, JZ7.2, 13.9 Hz, H-4), 3.15 (dd, 1H, JZ7.3,
13.9 Hz, H-4), 3.29 (d, 1H, JZ2.9 Hz, H-2), 3.49 (d, 1H,
JZ12.8 Hz, CH2Ph), 3.66 (dt, 1H, JZ2.9, 7.2 Hz, H-3),
3.69 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3), 3.86 (dq, 1H,
JZ7.2, 10.7 Hz, OCH2CH3), 3.88 (d, 1H, JZ12.8 Hz,
CH2Ph), 7.05–7.43 (m, 15H, Ph). 13C NMR d: 13.0
(OCH2CH3), 39.4 (C-4), 50.6 (C-3), 51.5 (CH2Ph), 59.8
(OCH2CH3), 61.3 (C-2), 125.4, 126.0, 126.5, 127.3, 127.4,
127.8, 128.2, 128.4, 129.1, 133.7, 138.6, 139.1 (Ph), 172.1
(C-1).
3.2.3. cis-Ethyl 1-benzyl-3-propylaziridine-2-carboxylate
1
3c.16 Oil, yieldZ61% (A), yieldZ67% (B). H NMR d:
0.80 (t, 3H, JZ7.2 Hz, CH2CH2CH3), 1.19 (t, 3H, JZ
7.2 Hz, OCH2CH3), 1.28–1.63 (m, 4H, CH2CH2CH3), 1.85
(q, 1H, JZ6.8 Hz, H-3), 2.17 (d, 1H, JZ6.8 Hz, H-2), 3.49
(d, 1H, JZ13.7 Hz, CH2Ph), 3.56 (d, 1H, JZ13.7 Hz,
CH2Ph), 4.13 (q, 2H, JZ7.2 Hz, OCH2CH3), 7.19–7.27 (m,
5H, Ph). 13C NMR d: 12.7 (CH2CH2CH3), 13.3
(OCH2CH3), 19.6 (CH2CH2CH3), 28.7 (CH2CH2CH3),
41.6 (C-2), 45.6 (C-3), 59.8 (OCH2CH3), 62.9 (CH2Ph),
126.1, 127.0, 127.3, 136.9 (Ph), 168.8 (C]O). Anal. Calcd
for C15H21NO2: C, 72.84; H, 8.56; N, 5.67. Found: C, 72.81;
H, 8.66; N, 5.89.
3.1.6. Ethyl 2-benzylamino-3-methyl-3-(phenylselanyl)-
1
butanoate 2f.16 Oil, yieldZ55%. H NMR d: 1.15 (t, 3H,
JZ7.1 Hz, OCH2CH3), 1.22 (s, 3H, H-4), 1.35 (s, 3H, H-4),
2.22 (s, 1H, NH), 3.21 (s, 1H, H-2), 3.55 (d, 1H, JZ13.1 Hz,
CH2Ph), 3.78 (d, 1H, JZ12.8 Hz, CH2Ph), 4.11 (q, 2H, JZ
7.1 Hz, OCH2CH3), 7.16–7.42 (m, 10H, Ph). 13C NMR d:
13.3 (OCH2CH3), 25.2 (C-4), 26.9 (C-4), 47.6 (C-3), 51.6
(CH2Ph), 59.6 (OCH2CH3), 68.3 (C-2), 126.1, 126.8, 127.0,
127.3, 127.5, 127.6, 137.4, 138.5 (Ph), 172.0 (C-1).
3.2. Cyclisation of b-(phenylselanyl)a-aminoesters 2
3.2.4.
cis-Ethyl
1-benzyl-3-iso-propylaziridine-
2-carboxylate 3d.16 Oil, yieldZ54% (A), yieldZ61%
1
Procedure A with Me3OBF4. To the b-(phenylselanyl)
a-aminoester 2 (1 mmol) in dichloromethane (10 mL) was
added Me3OBF4 (310 mg, 2.1 mmol) at room temperature.
After 12 h of stirring, the mixture was washed with a
(B). H NMR d: 0.72 (d, 3H, JZ6.2 Hz, CH(CH3)2), 0.79
(d, 3H, JZ6.2 Hz, CH(CH3)2), 1.15 (t, 3H, JZ7.1 Hz,
OCH2CH3), 1.48–1.53 (m, 2H, H-3, CH(CH3)2), 2.15 (d,
1H, JZ6.3 Hz, H-2), 3.43 (d, 1H, JZ13.9 Hz, CH2Ph), 3.47

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C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
(d, 1H, JZ13.9 Hz, CH2Ph), 4.10 (q, 2H, JZ7.1 Hz,
OCH2CH3), 7.10–7.25 (m, 5H, Ph). 13C NMR d: 13.3
(OCH2CH3), 18.6 (CH(CH3)2), 19.9 (CH(CH3)2), 26.2
(CH(CH3)2), 42.0 (C-2), 52.4 (C-3), 59.8 (OCH2CH3),
63.2 (CH2Ph), 127.5, 128.1, 128.6, 138.4 (Ph), 170.0
(C]O). Anal. Calcd for C15H21NO2: C, 72.84; H, 8.56;
N, 5.67. Found: C, 73.31; H, 8.99; N, 6.02.
4.28 (2!q, 2H, JZ7.2 Hz, OCH2CH3), 4.60, 4.62 (2!q,
1H, JZ6.4 Hz, CH(Ph)CH3), 6.95–7.42 (m, 10H, Ph).
3.3.1.4. Ethyl 2-((R)-1-phenylethylimino)-4-phenyl-3-
(phenylselanyl)butanoate 4e. Oil, two diastereomers:
50/50, conv.Z100%. 1H NMR d: 1.54–1.32 (m, 6H,
CH(Ph)CH3, OCH2CH3), 2.98–3.09 (m, 1H, H-4), 3.32–
3.45 (m, 1H, H-4), 4.16–4.29 (m, 3H, H-3, OCH2CH3),
4.58–4.69 (m, 1H, CH(Ph)CH3), 7.11–7.45 (m, 15H, Ph).
3.2.5. cis-Ethyl 1,3-dibenzylaziridine-2-carboxylate
1
3e.5b,16 Oil, yieldZ48% (A), yieldZ52% (B). H NMR d:
3.3.2. Reduction of a-(phenylselanyl)a-iminoesters 4.
The protocol is the same as the one for the synthesis of
a-(phenylselanyl)a-aminoesters 2.
1.18 (t, 3H, JZ7.1 Hz, OCH2CH3), 2.10 (q, 1H, JZ6.8 Hz,
H-3), 2.22 (d, 1H, JZ6.8 Hz, H-2), 2.77 (dd, 1H, JZ6.8,
14.7 Hz, CH2Ph), 2.98 (dd, 1H, JZ5.9, 14.7 Hz, CH2Ph),
3.48 (d, 1H, JZ13.7 Hz, CH2Ph), 3.56 (d, 1H, JZ13.7 Hz,
CH2Ph), 4.14 (q, 2H, JZ7.1 Hz, OCH2CH3), 7.07–7.23 (m,
10H, Ph). dC (75.4 MHz, CDCl3): 13.3 (OCH2CH3), 33.0
(CH2Ph), 41.4 (C-2), 46.4 (C-3), 60.0 (OCH2CH3), 62.6
(CH2Ph), 125.3, 126.1, 127.0, 127.3, 127.6, 128.4, 136.7,
137.7 (Ph), 168.6 (C]O).
3.3.2.1. Ethyl 2-((R)-1-phenylethylamino)-3-(phenyl-
selanyl)butanoate 5a, 50a. Oil, 5a/50a: 50/50, yieldZ47%.
(2R,3R)-Ethyl 2-((R)-1-phenylethylamino)-3-(phenyl-
1
selanyl)butanoate 50a. (First eluted). H NMR d: 1.19 (t,
3H, JZ7.2 Hz, OCH2CH3), 1.34 (d, 3H, JZ6.6 Hz,
CH(Ph)CH3), 1.46 (d, 3H, JZ6.9 Hz, H-4), 2.37 (s, 1H,
NH), 3.36 (d, 1H, JZ5.9 Hz, H-2), 3.57 (qd, 1H, JZ5.9,
6.9 Hz, H-3), 3.77 (q, 1H, JZ6.6 Hz, CH(Ph)CH3), 3.89 (q,
2H, JZ7.2 Hz, OCH2CH3), 7.25–7.52 (m, 10H, Ph). 13C
NMR d: 14.2 (OCH2CH3), 20.0 (C-4), 23.3 (CH(Ph)CH3),
43.3 (C-3), 57.5 (CH(Ph)CH3), 61.0 (OCH2CH3), 64.5
(C-2), 127.2, 127.3, 127.7, 128.5, 128.9, 129.1, 135.3, 145.4
(Ph), 173.4 (C-1). [a]2D5 C14.8 (c 1.0 in CHCl3).
3.2.6. Ethyl 1-benzyl-3,3-dimethylaziridine-2-carboxylate
3f. Oil, yieldZ65% (B). 1H NMR d: 1.20 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.26 (s, 3H, CH3), 1.28 (s, 3H, CH3), 2.05 (s,
1H, H-2), 3.68 (d, 1H, JZ14.8 Hz, CH2Ph), 3.75 (d, 1H, JZ
14.8 Hz, CH2Ph), 4.14 (q, 2H, JZ7.2 Hz, OCH2CH3), 7.15–
7.26 (m, 5H, Ph). 13C NMR d: 14.5 (OCH2CH3), 18.0
(CH3), 21.9 (CH3), 44.8 (C-3), 49.4 (C-2), 56.0 (CH2Ph),
60.9 (OCH2CH3), 126.8, 127.4, 128.4, 139.3 (Ph), 170.4
(C]O). Anal. Calcd for C14H19NO2: C, 72.07; H, 8.21; N,
6.00. Found: C, 72.14; H, 7.79; N, 6.34.
(2S,3S)-Ethyl
2-((R)-1-phenylethylamino)-3-(phenyl-
1
selanyl)butanoate 5a. (Second eluted). H NMR d: 1.14 (t,
3H, JZ7.2 Hz, OCH2CH3), 1.37 (d, 3H, JZ6.9 Hz, H-4),
1.38 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 2.19 (s, 1H, NH), 3.09
(d, 1H, JZ5.1 Hz, H-2), 3.54 (qd, 1H, JZ5.1, 6.9 Hz, H-3),
3.73 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.01 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 4.18 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 7.23–7.47 (m, 10H, Ph). 13C NMR d: 14.3
(OCH2CH3), 20.5 (C-4), 25.4 (CH(Ph)CH3), 43.2 (C-3),
57.0 (CH(Ph)CH3), 60.9 (OCH2CH3), 63.9 (C-2), 126.9,
127.2, 127.7, 128.5, 128.9, 129.1, 135.2, 145.4 (Ph), 173.7
(C-1). [a]2D5 K17.1 (c 1.0 in CHCl3).
3.3. Synthesis of b-(phenylselanyl)a-aminoesters 5
3.3.1. Preparation of b-(phenylselanyl)a-iminoesters 4.
The protocol is the same as the one for the synthesis of
a-(phenylselanyl)a-aminoesters 2. The b-(phenylselanyl)
a-iminoesters 4 were isolated but not purified because of
decomposition. That is why we just reported their 1H NMR
spectrum.
3.3.1.1. Ethyl-2-((R)-1-phenylethylimino)-3-(phenyl-
selanyl)butanoate 4a. Oil, two diastereomers: 50/50,
conv.Z100%. 1H NMR d: 1.34–1.63 (m, 9H, H-4,
CH(Ph)CH3, OCH2CH3), 4.14, 4.16 (2!q, 1H, JZ6.9 Hz,
H-3), 4.30–4.40 (m, 2H, OCH2CH3), 4.70, 4.73 (2!q, 1H,
JZ6.4 Hz, CH(Ph)CH3), 7.24–7.65 (m, 10H, Ph).
3.3.2.2. Ethyl 2-((R)-1-phenylethylamino)-3-(phenyl-
selanyl)pentanoate 5b, 50b. Oil, 5b/50b: 50/50, yieldZ
53%.
(2S,3S)-Ethyl
2-((R)-1-phenylethylamino)-3-(phenyl-
1
selanyl)pentanoate 5b. (First eluted). H NMR d: 0.86 (t,
3H, JZ7.2 Hz, H-5), 1.08 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.40 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.64–1.92 (m, 2H,
H-4), 2.28 (s, 1H, NH), 3.24 (d, 1H, JZ3.3 Hz, H-2), 3.39
(td, 1H, JZ3.3, 7.2 Hz, H-3), 3.62–3.78 (m, 2H, OCH2CH3,
CH(Ph)CH3), 3.82–2.92 (m, 1H, OCH2CH3), 7.09–7.48 (m,
10H, Ph). 13C NMR d: 12.8 (C-5), 14.1 (OCH2CH3), 25.3
(CH(Ph)CH3), 27.4 (C-4), 53.1 (C-3), 56.9 (CH(Ph)CH3)
60.7 (OCH2CH3), 61.8 (C-2), 127.2, 127.4, 127.5, 128.4,
128.9, 130.0, 134.7, 145.4 (Ph), 173.7 (C-1). [a]2D5 K16.3 (c
1.0, CHCl3).
3.3.1.2. Ethyl 2-((R)-1-phenylethylimino)-3-(phenyl-
selanyl)pentanoate 4b. Oil, two diastereomers: 50/50,
conv.Z100%. H NMR d: 0.98 (t, 3H, JZ7.4 Hz, H-5),
1.19–1.31 (m, 6H, CH(Ph)CH3, OCH2CH3), 1.68–1.78 (m,
1H, H-4), 1.90–2.02 (m, 1H, H-4), 3.83, 3.88 (2!t, 1H, JZ
7.4 Hz, H-3), 4.23, 4.28 (2!q, 2H, JZ7.2 Hz, OCH2CH3),
4.60, 4.62 (2!q, 1H, JZ6.4 Hz, CH(Ph)CH3), 6.95–7.45
(m, 10H, Ph).
1
3.3.1.3. Ethyl 2-((R)-1-phenylethylimino)-3-(phenyl-
selanyl)hexanoate 4c. Oil, two diastereomers: 50/50,
conv.Z100%. 1H NMR d: 0.83, 0.85 (2!t, 3H, JZ
7.2 Hz, H-6), 1.19–1.31 (m, 6H, CH(Ph)CH3, OCH2CH3),
1.32–1.60 (m, 2H, H-5), 1.62–1.89 (m, 1H, H-4), 1.87–2.03
(m, 1H, H-4), 3.88, 3.93 (2!t, 1H, JZ7.9 Hz, H-3), 4.23,
(2R,3R)-Ethyl 2-((R)-1-phenylethylamino)-3-(phenyl-
1
selanyl)pentanoate 50b. (Second eluted). H NMR d: 1.08
(t, 3H, JZ7.2 Hz, OCH2CH3), 1.11 (t, 3H, JZ7.2 Hz, H-5),
1.34 (d, 3H, JZ6.6 Hz, CH(Ph)CH3), 1.81–1.98 (m, 2H,

C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
2663
H-4), 2.38 (s, 1H, NH), 3.41 (ddd, 1H, JZ4.1, 6.4, 7.7 Hz,
H-3), 3.53 (d, 1H, JZ4.1 Hz, H-2), 3.72–3.78 (m, 2H,
CH(Ph)CH3, OCH2CH3), 3.79–3.84 (m, 1H, OCH2CH3),
7.24–7.54 (m, 10H, Ph). 13C NMR d: 12.9 (C-5), 14.1
(OCH2CH3), 23.3 (CH(Ph)CH3), 37.2 (C-4), 53.3 (C-3),
57.3 (CH(Ph)CH3), 60.9 (OCH2CH3), 62.2 (C-2), 126.8,
127.2, 127.4, 128.4, 128.9, 134.4, 134.7, 145.6 (Ph), 173.5
(C-1). [a]2D5 C12.1 (c 1.0, CHCl3).
1H, JZ3.1 Hz, H-2), 3.73–3.79 (m, 3H, H-3, CH(Ph)CH3,
OCH2CH3), 3.87 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
7.15–7.42 (m, 15H, Ph). 13C NMR d: 14.0 (OCH2CH3), 23.0
(CH(Ph)CH3), 40.4 (C-4), 51.9 (C-3), 56.9 (CH(Ph)CH3),
60.9 (OCH2CH3), 61.1 (C-2), 126.5, 126.8, 127.1, 127.4,
127.5, 128.1, 128.3, 128.5, 129.4, 134.8, 139.7, 145.5 (Ph),
173.2 (C-1). [a]2D5 C13.6 (c 1.0 in CHCl3).
3.4. Cyclisation of b-(phenylselanyl)a-aminoesters 5, 50
3.3.2.3. Ethyl 2-((R)-1-phenylethylamino)-3-(phenyl-
selanyl)hexanoate 5c, 50c. Oil, 5c/50c: 50/50, yieldZ51%.
The protocols are the same as for the cyclisation of b-
(phenylselanyl)a-aminoesters 2.
(2S,3S)-Ethyl
2-((R)-1-phenylethylamino)-3-(phenyl-
1
Procedure A with Me3OBF4. b-(Phenylselanyl)a-amino-
esters 5 (or 50) afforded aziridines 6 (or 60).
selanyl)hexanoate 5c. (First eluted). H NMR d: 0.71 (t,
3H, JZ7.2 Hz, H-6), 0.98 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.18–1.32 (m, 2H, H-5), 1.30 (d, 3H, JZ6.4 Hz,
CH(Ph)CH3), 1.57–1.73 (m, 2H, H-4), 2.16 (s, 1H, NH),
3.11 (d, 1H, JZ3.3 Hz, H-2), 3.83 (td, 1H, JZ3.3, 7.2 Hz,
H-3), 3.63 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3), 3.68 (q,
1H, JZ6.4 Hz, CH(Ph)CH3), 3.86 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 7.11–7.41 (m, 10H, Ph). 13C NMR
d: 13.7 (C-6), 14.1 (OCH2CH3), 21.2 (C-5), 25.3
(CH(Ph)CH3), 36.4 (C-4), 50.7 (C-3), 57.0 (CH(Ph)CH3),
60.8 (OCH2CH3), 61.9 (C-2), 127.2, 127.4, 127.5, 128.4,
129.0, 130.1, 134.7, 145.5 (Ph), 173.8 (C-1). [a]2D5 K14.2
(c 1.0 in CHCl3).
Procedure B with NBS. b-(Phenylselanyl)a-aminoester 5
(or 50) afforded aziridines 6 (or 60), except for 5a, which lead
to 600a.
3.4.1. (2R,3R)-Ethyl 3-methyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 6a.5b Oil, yieldZ47% (A). 1H
NMR d: 1.11 (d, 3H, JZ5.6 Hz, CH3), 1.23 (t, 3H, JZ
7.2 Hz, OCH2CH3), 1.37 (d, 3H, JZ6.4 Hz, CH(Ph)CH3),
1.78–1.82 (m, 1H, H-3), 2.15 (d, 1H, JZ6.6 Hz, H-2), 2.56
(q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.15 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 4.17 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 7.17–7.33 (m, 5H, Ph). 13C NMR d: 13.3
(CH3), 14.6 (OCH2CH3), 23.1 (CH(Ph)CH3), 41.3 (C-3),
43.3 (C-2), 61.0 (OCH2CH3), 69.8 (CH(Ph)CH3), 126.9,
127.2, 128.5, 143.9 (Ph), 170.0 (C]O). MS m/z: 233 (MC,
2), 128 (68), 105 (100). IR nmax (neat) cmK1: 2967, 1744,
1450, 1186. Anal. Calcd for C14H19NO2: C, 72.10; H, 8.21;
N, 6.00. Found: C, 72.45; H, 8.19; N, 6.33. [a]2D5 C57.3 (c
1.0 in CH2Cl2).
(2R,3R)-Ethyl 2-((R)-1-phenylethylamino)-3-(phenyl-
1
selanyl)hexanoate 50c. (Second eluted). H NMR d: 0.84
(t, 3H, JZ7.2 Hz, H-6), 0.98 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.24 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.31–1.61 (m, 2H,
H-5), 1.68–1.85 (m, 2H, H-4), 2.29 (s, 1H, NH), 3.36–3.43
(m, 2H, H-2, H-3), 3.67–3.82 (m, 3H, CH(Ph)CH3,
OCH2CH3), 7.15–7.45 (m, 10H, Ph). 13C NMR d: 13.9
(C-6), 14.1 (OCH2CH3), 21.3 (C-5), 23.4 (CH(Ph)CH3),
36.3 (C-4), 51.1 (C-3), 57.3 (CH(Ph)CH3), 60.9
(OCH2CH3), 62.5 (C-2), 126.9, 127.2, 127.3, 127.4, 128.4,
128.5, 134.7, 145.7 (Ph), 173.5 (C-1). [a]2D5 C11.7 (c 1.0 in
CHCl3).
3.4.2. (2S,3S)-Ethyl 3-methyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 60a.5b Oil, yieldZ49% (A),
yieldZ51% (B). 1H NMR d: 1.13 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.28 (d, 3H, JZ5.4 Hz, CH3), 1.36 (d, 3H, JZ
6.6 Hz, CH(Ph)CH3), 1.94–2.00 (m, 1H, H-3), 2.02 (d, 1H,
JZ6.9 Hz, H-2), 2.57 (q, 1H, JZ6.6 Hz, CH(Ph)CH3), 4.06
(dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3), 4.08 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 7.15–7.31 (m, 5H, Ph). 13C NMR d:
13.8 (CH3), 14.5 (OCH2CH3), 23.9 (CH(Ph)CH3), 42.4 (C-
3), 42.7 (C-2), 59.9 (OCH2CH3), 69.8 (CH(Ph)CH3), 126.7,
127.1, 128.5, 143.3 (Ph), 168.1 (C]O). MS m/z: 233 (MC,
2), 128 (84), 105 (100). IR nmax (neat) cmK1: 2967, 1744,
1450, 1186. Anal. Calcd for C14H19NO2: C, 72.10; H, 8.21;
N, 6.00. Found: C, 71.81; H, 8.08; N, 6.13. [a]2D5 K20.9 (c
1.0 in CH2Cl2).
3.3.2.4. Ethyl 2-((R)-1-phenylethylamino)-4-phenyl-3-
(phenylselanyl)butanoate 5e, 50e. Oil, 5e/50e: 50/50,
yieldZ50%.
(2S,3S)-Ethyl 2-((R)-1-phenylethylamino)-4-phenyl-3-
(phenylselanyl)butanoate 5e. (First eluted). 1H NMR d:
0.95 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.35 (d, 3H, JZ6.6 Hz,
CH(Ph)CH3), 2.39 (s, 1H, NH), 2.86 (dd, 1H, JZ6.9,
14.1 Hz, H-4), 2.99 (dd, 1H, JZ7.9, 14.1 Hz, H-4), 3.18 (d,
1H, JZ2.8 Hz, H-2), 3.47–3.51 (m, 1H, H-3), 3.65–3.69 (m,
2H, CH(Ph)CH3, OCH2CH3), 3.84 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 6.78–7.22 (m, 15H, Ph). 13C NMR
d: 14.1 (OCH2CH3), 25.2 (CH(Ph)CH3), 39.8 (C-4), 52.9
(C-3), 57.2 (CH(Ph)CH3), 59.9 (OCH2CH3), 61.9 (C-2),
126.3, 127.2, 127.3, 127.5, 127.7, 128.3, 128.4, 128.9,
129.4, 134.8, 139.8, 145.4 (Ph), 173.6 (C-1). [a]2D5 K15.4 (c
1.0 in CHCl3).
3.4.3. (2R,3R)-Ethyl 1-((R)-1-phenylethyl)-3-ethyl-
aziridine-2-carboxylate 6b. Oil, yieldZ50% (A), yieldZ
55%(B). 1H NMR d: 0.58 (t, 3H, JZ7.4 Hz, CH2CH3), 1.25
(t, 3H, JZ7.2 Hz, OCH2CH3), 1.39 (d, 3H, JZ6.6 Hz,
CH(Ph)CH3), 1.38–1.55 (m, 2H, CH2CH3), 1.70 (q, 1H, JZ
6.6 Hz, H-3), 2.17 (d, 1H, JZ6.6 Hz, H-2), 2.53 (q, 1H, JZ
6.6 Hz, CH(Ph)CH3), 4.16 (dq, 2H, JZ7.2, 12.3 Hz,
OCH2CH3), 7.16–7.41 (m, 5H, Ph). 13C NMR d: 11.4
(CH2CH3), 14.4 (OCH2CH3), 21.2 (CH2CH3), 22.6
(CH(Ph)CH3), 43.0 (C-2), 47.7 (C-3), 60.9 (OCH2CH3),
70.0 (CH(Ph)CH3), 127.2, 127.3, 128.3, 143.6 (Ph), 170.0
(2R,3R)-Ethyl 2-((R)-1-phenylethylamino)-4-phenyl-3-
1
(phenylselanyl)butanoate 50e. (Second eluted). H NMR d:
1.04 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.26 (d, 3H, JZ6.4 Hz,
CH(Ph)CH3), 2.37 (s, 1H, NH), 3.21 (dd, 1H, JZ7.4,
14.1 Hz, H-4), 3.30 (dd, 1H, JZ7.9, 14.1 Hz, H-4), 3.49 (d,

2664
C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
(C]O). MS m/z: 247 (MC, 16), 142 (16), 105 (100). IR
nmax (neat) cmK1: 2968, 1744, 1451, 1185. Anal. Calcd for
C15H21NO2: C, 58.29; H, 8.50; N, 5.66. Found: C, 58.39; H,
8.71; N, 5.48. [a]2D5 C56.9 (c 1.0, CH2Cl2).
CH2Ph), 2.85 (dd, 1H, JZ5.4, 14.7 Hz, CH2Ph), 4.16 (q,
2H, JZ7.2 Hz, OCH2CH3), 6.88–7.28 (m, 10H, Ph). 13C
NMR d: 14.4 (OCH2CH3), 22.7 (CH(Ph)CH3), 34.2
(CH2Ph), 42.8 (C-2), 47.1 (C-3), 61.1 (OCH2CH3), 70.1
(CH(Ph)CH3), 126.2, 126.7, 127.2, 127.4, 128.5, 128.7,
138.8, 143.4 (Ph), 170.0 (C]O). MS m/z: 309 (MC, 1), 218
(11), 130 (100), 105 (72). IR nmax (neat) cmK1: 2968, 1743,
1455, 1183. Anal. Calcd for C20H23NO2: C, 77.60; H, 7.49;
N, 4.53. Found: C, 77.89; H, 7.53; N, 4.68. [a]2D5 C36.1 (c
1.0 in CH2Cl2).
3.4.4. (2S,3S)-Ethyl 1-((R)-1-phenylethyl)-3-ethyl-
aziridine-2-carboxylate 60b. Oil, yieldZ56% (A),
yieldZ49% (B). 1H NMR d: 0.97 (t, 3H, JZ7.4 Hz,
CH2CH3), 1.16 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.38 (d, 3H,
JZ6.6 Hz, CH(Ph)CH3), 1.39–1.73 (m, 2H, CH2CH3), 1.84
(dt, 1H, JZ6.9, 6.1 Hz, H-3), 2.05 (d, 1H, JZ6.9 Hz, H-2),
2.56 (q, 1H, JZ6.6 Hz, CH(Ph)CH3), 4.07 (dq, 1H, JZ7.2,
10.5 Hz, OCH2CH3), 4.09 (dq, 1H, JZ7.2, 10.5 Hz,
OCH2CH3), 7.11–7.41 (m, 5H, Ph). 13C NMR d: 11.9
(CH2CH3), 14.3 (OCH2CH3), 21.4 (CH2CH3), 23.8
(CHaCH3), 42.5 (C-2), 48.9 (C-3), 60.8 (OCH2CH3), 69.5
(CH(Ph)CH3), 126.6, 127.0, 128.4, 143.8 (Ph), 169.7
(C]O). MS m/z: 247 (MC, 2), 142 (100), 105 (84). IR
nmax (neat) cmK1: 2967, 1744, 1450, 1186. Anal. Calcd for
C15H21NO2: C, 58.29; H, 8.50; N, 5.66. Found: C, 58.72; H,
8.84; N, 5.27. [a]2D5 K19.1 (c 1.0, CH2Cl2).
3.4.8. (2S,3S)-Ethyl 3-benzyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 60e.5b Oil, yieldZ44% (A),
yieldZ52% (B). 1H NMR d: 1.13 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.20 (d, 3H, JZ6.6 Hz, CH(Ph)CH3), 2.08–
2.12 (m, 1H, H-3), 2.10 (d, 1H, JZ6.6 Hz, H-2), 2.55 (q,
1H, JZ6.6 Hz, CH(Ph)CH3), 2.85 (dd, 1H, JZ4.6, 14.3 Hz,
CH2Ph), 2.99 (dd, 1H, JZ4.3, 14.3 Hz, CH2Ph), 4.09 (dq,
1H, JZ7.2, 10.7 Hz, OCH2CH3), 4.12 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 7.17–7.28 (m, 10H, Ph). 13C NMR d:
14.4 (OCH2CH3), 23.8 (CH(Ph)CH3), 34.7 (CH2Ph), 42.5
(C-2), 48.5 (C-3), 59.9 (OCH2CH3), 69.6 (CH(Ph)CH3),
126.6, 126.7, 127.2, 128.5, 128.6, 129.0, 139.1, 139.8 (Ph),
169.6 (C]O). MS m/z: 309 (MC, 1), 218 (11), 130 (100),
105 (72). IR nmax (neat) cmK1: 2968, 1743, 1455, 1183.
Anal. Calcd for C20H23NO2: C, 77.60; H, 7.49; N, 4.53.
Found: C, 77.92; H, 7.74; N, 4.76. [a]2D5 K11.3 (c 1.0 in
CH2Cl2).
3.4.5. (2R,3R)-Ethyl 1-((R)-1-phenylethyl)-3-propyl-
aziridine-2-carboxylate 6c. Oil, yieldZ55% (A), yieldZ
61% (B). 1H NMR d: 0.64 (t, 3H, JZ7.4 Hz, CH2CH2CH3),
0.95–1.08 (m, 2H, CH2CH2CH3), 1.21 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.38–1.54 (m, 2H, CH2CH2CH3), 1.40 (d, 3H,
JZ6.4 Hz, CH(Ph)CH3), 1.70–1.76 (m, 1H, H-3), 2.15 (d,
1H, JZ6.9 Hz, H-2), 2.51 (q, 1H, JZ6.4 Hz, CH(Ph)CH3),
4.14 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3), 4.16 (dq, 1H,
JZ7.2, 10.7 Hz, OCH2CH3), 7.23–7.32 (m, 5H, Ph). 13C
NMR d: 13.7 (CH2CH2CH3), 14.4 (OCH2CH3), 20.5
(CH2CH2CH3), 22.7 (CH(Ph)CH3), 29.9 (CH2CH2CH3),
43.2 (C-2), 46.1 (C-3), 60.9 (OCH2CH3), 70.2
(CH(Ph)CH3), 127.3, 127.4, 128.4, 143.7 (Ph), 170.1
(C]O). MS m/z: 261 (MC, 5), 156 (100), 105 (81), 82
(49). IR nmax (neat) cmK1: 2978, 1744, 1453, 1184. Anal.
Calcd for C16H23NO2: C, 73.53; H, 8.87; N, 5.36. Found: C,
73.69; H, 9.07; N, 5.38. [a]2D5 C41.2 (c 1.0 in CH2Cl2).
3.5. Synthesis of b-aminoesters 11
n-Butyllithium 2.5 M in hexane (5.4 mL, 13 mmol,
1.3 equiv) was added dropwise to a solution of (R)-N-
benzyl-N-((R)-1-phenylethyl)amine (2.74 g, 13 mmol,
1.3 equiv) in THF (75 mL) at 0 8C under argon. After
15 min at 0 8C, the mixture was cooled to K78 8C. a,b-
Unsaturated ester 10 (10 mmol, 1 equiv) in solution in THF
(5 mL) was then introduced. After 40 min of stirring at
K78 8C, the mixture was quenched with a saturated
aqueous solution of ammonium chloride (5 mL) and
allowed to reach room temperature. Water (90 mL) and
ether (30 mL) were added. The aqueous phase was
separated and extracted with ether (2!80 mL). The
combined organic phases were washed with an aqueous
solution of hydrochloric acid 0.5 N (200 mL) and then with
a saturated aqueous solution of sodium chloride (200 mL).
After drying over MgSO4 and concentration, the crude
product was purified by silica gel chromatography (cyclo-
hexane/ether: 90:10).
3.4.6. (2S,3S)-Ethyl 1-((R)-1-phenylethyl)-3-propyl-
aziridine-2-carboxylate 60c. Oil, yieldZ52% (A),
yieldZ58% (B). 1H NMR d: 0.90 (t, 3H, JZ7.2 Hz,
CH2CH2CH3), 1.14 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.18–
1.63 (m, 4H, CH2CH2CH3), 1.38 (d, 3H, JZ6.4 Hz,
CH(Ph)CH3), 1.84–1.91 (m, 1H, H-3), 2.05 (d, 1H, JZ
6.9 Hz, H-2), 2.56 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.08
(dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3), 4.11 (dq, 1H, JZ7.2,
10.7 Hz, OCH2CH3), 7.16–7.32 (m, 5H, Ph). 13C NMR d:
14.0 (CH2CH2CH3), 14.4 (OCH2CH3), 21.0 (CH2CH2CH3),
23.8 (CH(Ph)CH3), 30.2 (CH2CH2CH3), 42.5 (C-2), 47.4
(C-3), 60.8 (OCH2CH3), 69.7 (CH(Ph)CH3), 126.7, 127.1,
3.5.1. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)butanoate 11a.24 Oil, yieldZ79%. 1H NMR d:
1.18 (d, 3H, JZ6.6 Hz, H-4), 1.20 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.39 (d, 3H, JZ6.9 Hz, CH(Ph)CH3), 2.15 (dd,
1H, JZ7.9, 14.1 Hz, H-2), 2.40 (dd, 1H, JZ5.9, 14.1 Hz,
H-2), 3.46–3.53 (m, 1H, H-3), 3.73 (d, 1H, JZ14.6 Hz,
CH2Ph), 3.77 (d, 1H, JZ14.6 Hz, CH2Ph), 3.94–4.03 (m,
2H, CH(Ph)CH3, OCH2CH3), 4.08 (dq, 1H, JZ7.2,
10.8 Hz, OCH2CH3), 7.26–7.48 (m, 10H, Ph). 13C NMR
d: 14.2 (OCH2CH3), 18.0 (CH(Ph)CH3), 18.7 (C-4), 39.9
(C2), 49.7 (CH2Ph), 50.2 (C-3), 57.8 (CH(Ph)CH3), 60.2
(OCH2CH3), 126.7, 126.9, 127.8, 128.1, 128.2, 128.4,
141.9, 144.4 (Ph), 172.5 (C-1). Anal. Calcd for
128.3, 143.9 (Ph), 169.7 (C]O). IR nmax (neat) cmK1
:
2978, 1744, 1453, 1184. Anal. Calcd for C16H23NO2: C,
73.53; H, 8.87; N, 5.36. Found: C, 73.85; H, 9.12; N, 5.54.
[a]2D5 K18.4 (c 1.0 in CH2Cl2).
3.4.7. (2R,3R)-Ethyl 3-benzyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 6e.5b Oil, yieldZ41% (A),
yieldZ48% (B). 1H NMR d: 1.20 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.38 (d, 3H, JZ6.6 Hz, CH(Ph)CH3), 2.00–
2.05 (m, 1H, H-3), 2.22 (d, 1H, JZ6.4 Hz, H-2), 2.57 (q,
1H, JZ6.6 Hz, CH(Ph)CH3), 2.73 (dd, 1H, JZ7.3, 14.7 Hz,

C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
2665
C21H27NO2: C, 77.50; H, 8.36; N, 4.30. Found: C, 77.72; H,
8.56; N, 4.61. [a]2D5 C4.9 (c 1.0 in CHCl3).
141.3, 143.2 (Ph), 172.6 (C-1). Anal. Calcd for C27H31NO2:
C, 80.76; H, 7.78; N, 3.49. Found: C, 81.02; H, 8.04; N,
3.76. [a]2D5 C3.9 (c 1.0 in CHCl3).
3.5.2. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)pentanoate 11b. Oil, yieldZ75%. 1H NMR d:
0.93 (t, 3H, JZ7.2 Hz, H-5), 1.11 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.28 (d, 3H, JZ6.9 Hz, CH(Ph)CH3), 1.40–
1.50 (m, 2H, H-4), 1.92 (d, 2H, JZ6.4 Hz, H-2), 3.12–3.21
(m, 1H, H-3), 3.46 (d, 1H, JZ14.9 Hz, CH2Ph), 3.71 (d, 1H,
JZ14.9 Hz, CH2Ph), 3.76 (q, 1H, JZ6.9 Hz, CH(Ph)CH3),
3.5.6. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)-3-phenylpropanoate 11g. Oil, yieldZ89%. 1H
NMR d: 0.96 (t, 3H, JZ6.9 Hz, OCH2CH3), 1.15 (d, 3H,
JZ6.7 Hz, CH(Ph)CH3), 2.47 (dd, 1H, JZ9.4, 14.6 Hz,
H-2), 2.58 (dd, 1H, JZ5.6, 14.6 Hz, H-2), 3.58 (d, 1H, JZ
14.6 Hz, CH2Ph), 3.66 (d, 1H, JZ14.6 Hz, CH2Ph), 3.65 (q,
2H, JZ6.9 Hz, OCH2CH3), 3.93 (q, 1H, JZ6.7 Hz,
CH(Ph)CH3), 4.36 (dd, 1H, JZ5.6, 9.4 Hz, H-3), 7.17–
7.33 (m, 15H, Ph). 13C NMR d: 14.1 (OCH2CH3), 16.0
(CH(Ph)CH3), 37.9 (C-2), 51.0 (CH2Ph), 57.0
(CH(Ph)CH3), 59.6 (C-3), 60.4 (OCH2CH3), 126.7, 126.9,
127.3, 127.9, 128.2, 128.3, 141.6, 141.9, 144.2 (Ph), 171.9
(C-1). Anal. Calcd for C29H25NO2: C, 80.59; H, 7.54; N,
3.61. Found: C, 80.94; H, 7.69; N, 3.87. [a]2D5 C6.8 (c 1.0 in
CHCl3).
3.87–4.00 (m, 2H, OCH2CH3), 7.15–7.40 (m, 10H, Ph). 13
C
NMR d: 12.1, 14.3 (C-5, OCH2CH3), 19.7 (CH(Ph)CH3),
26.4 (C-4), 36.9 (C-2), 50.1 (CH2Ph), 55.8 (C-3), 57.8
(CH(Ph)CH3), 60.2 (OCH2CH3), 126.7, 127.0, 128.1, 128.2,
128.4, 141.8, 143.2 (Ph), 173.1 (C-1). Anal. Calcd for
C22H29NO2: C, 77.83; H, 8.61; N, 4.12. Found: C, 77.52; H,
8.46; N, 3.87. [a]2D5 C4.3 (c 1.0 in CHCl3).
3.5.3. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
1
amino)hexanoate 11c.24,25 Oil, yieldZ72%. H NMR d:
0.79 (t, 3H, JZ7.2 Hz, H-6), 1.11 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.15–1.21 (m, 1H, H-5), 1.26 (d, 3H, JZ
6.9 Hz, CH(Ph)CH3), 1.47–1.53 (m, 3H, H-4, H-5), 1.90
(dd, 1H, JZ8.2, 14.6 Hz, H-2), 1.97 (dd, 1H, JZ4.9,
14.6 Hz, H-2), 3.18–3.31 (m, 1H, H-3), 3.46 (d, 1H, JZ
14.9 Hz, CH2Ph), 3.71 (d, 1H, JZ14.9 Hz, CH2Ph), 3.75 (q,
1H, JZ6.9 Hz, CH(Ph)CH3), 3.89 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 3.94 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
7.15–7.37 (m, 10H, Ph). 13C NMR d: 14.2, 14.3 (C-6,
OCH2CH3), 19.9 (CH(Ph)CH3), 20.3 (C-5), 36.0 (C-4), 37.0
(C-2), 50.2 (CH2Ph), 54.0 (C-3), 58.1 (CH(Ph)CH3), 60.2
(OCH2CH3), 126.7, 127.0, 127.4, 128.1, 128.2, 128.4,
142.0, 143.4 (Ph), 173.1 (C-1). [a]2D5 C4.1 (c 1.0 in CHCl3).
3.6. Synthesis of b-aminoesters 12
Cerium and ammonium nitrate (5.74 g, 10.5 mmol,
2.1 equiv) was added to b-amino ester 11 (5 mmol,
1 equiv) in a mixture of acetonitrile/water: 5:1 (50 mL) at
0 8C. After 1 h of stirring at room temperature, a saturated
aqueous solution of sodium carbonate (40 mL) was
introduced. The solid was filtered and washed with ether
(2!25 mL). The aqueous phase was separated and
extracted with ether (2!40 mL). The combined organic
phases were dried over MgSO4 and concentrated. The crude
product was purified by silica gel chromatography (cyclo-
hexane/ether: 70:30).
3.6.1. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)butanoate
12a.26 Oil, yieldZ68%. 1H NMR d: 0.97 (d, 3H, JZ6.6 Hz,
H-4), 1.17 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.24 (d, 3H, JZ
6.4 Hz, CH(Ph)CH3), 2.30 (dd, 1H, JZ6.4, 14.6 Hz, H2),
2.35 (dd, 1H, JZ5.6, 14.6 Hz, H-2), 2.86–2.94 (m, 1H,
H-3), 3.80 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.05 (q, 2H, JZ
7.2 Hz, OCH2CH3), 7.17–7.25 (m, 5H, Ph). 13C NMR d:
14.4 (OCH2CH3), 21.6 (C-4), 24.7 (CH(Ph)CH3), 41.0
(C-2), 47.9 (C-3), 55.1 (CH(Ph)CH3), 60.3 (OCH2CH3),
126.6, 127.0, 128.5, 146.2 (Ph), 172.4 (C-1). [a]2D5 C31.1
(c 1.0, CHCl3).
3.5.4. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)-4-methylpentanoate 11d. Oil, yieldZ82%. 1H
NMR d: 0.85 (d, 3H, JZ6.6 Hz, H-5), 1.08 (d, 3H, JZ
6.6 Hz, H-5), 1.20 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.37 (d,
3H, JZ6.9 Hz, CH(Ph)CH3), 1.62–1.79 (m, 1H, H-4), 1.89
(dd, 1H, JZ2.3, 15.9 Hz, H-2), 2.06 (dd, 1H, JZ9.2,
15.9 Hz, H-2), 3.17–3.29 (m, 1H, H-3), 3.50 (d, 1H, JZ
14.8 Hz, CH2Ph), 3.75 (q, 1H, JZ6.9 Hz, CH(Ph)CH3),
3.78 (d, 1H, JZ14.8 Hz, CH2Ph), 4.04 (q, 2H, JZ7.2 Hz,
OCH2CH3), 7.18–7.50 (m, 10H, Ph). 13C NMR d: 14.3
(OCH2CH3), 19.7 (C-5), 20.3 (CH(Ph)CH3), 21.1 (C-5),
32.9 (C-4), 35.0 (C-2), 51.4 (CH2Ph), 58.1 (CH(Ph)CH3),
58.6 (C-3), 60.2 (OCH2CH3), 126.1, 126.7, 127.1, 128.7,
141.7, 142.4 (Ph), 173.4 (C-1). Anal. Calcd for C23H31NO2:
C, 78.15; H, 8.84; N, 3.96. Found: C, 78.42; H, 9.13; N,
4.22. [a]2D5 C5.3 (c 1.0 in CHCl3).
3.6.2. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-
pentanoate 12b. Oil, yieldZ66%. 1H NMR d: 0.78 (t,
3H, JZ7.4 Hz, H-5), 1.18 (t, 3H, JZ7.1 Hz, OCH2CH3),
1.24 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.31–1.38 (m, 2H, H-
4), 1.45 (s, 1H, NH), 2.28 (dd, 1H, JZ5.6, 14.6 Hz, H-2),
2.38 (dd, 1H, JZ5.9, 14.6 Hz, H-2), 2.60–2.69 (m, 1H, H-
3), 3.81 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.06 (q, 2H, JZ
7.1 Hz, OCH2CH3), 7.14–7.30 (m, 5H, Ph). 13C NMR d:
10.5 (C-5), 14.4 (OCH2CH3), 25.0 (CH(Ph)CH3), 28.1 (C-
4), 38.4 (C-2), 53.7 (C-3), 55.2 (CH(Ph)CH3), 60.3
(OCH2CH3), 126.8, 127.0, 128.5, 146.2 (Ph), 172.7 (C-1).
[a]2D5 C29.3 (c 1.0, CHCl3).
3.5.5. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)-4-phenylbutanoate 11e. Oil, yieldZ78%. 1H
NMR d: 1.09 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.12 (d, 3H,
JZ6.9 Hz, CH(Ph)CH3), 2.03 (d, 2H, JZ6.9 Hz, H-4), 2.55
(dd, 1H, JZ6.9, 13.6 Hz, H-2), 2.79 (dd, 1H, JZ7.0,
13.6 Hz, H-2), 3.54–3.67 (m, 1H, H-3), 3.57 (d, 1H, JZ
14.8 Hz, CH2Ph), 3.76–3.98 (m, 3H, CH(Ph)CH3,
OCH2CH3), 3.82 (d, 1H, JZ14.8 Hz, CH2Ph), 7.09–7.32
(m, 15H, Ph). 13C NMR d: 14.2 (OCH2CH3), 19.0
(CH(Ph)CH3), 36.9 (C-4), 39.8 (C-2), 50.1 (CH2Ph), 56.6
(C-3), 57.8 (CH(Ph)CH3), 60.2 (OCH2CH3), 126.1, 126.8,
127.0, 128.0, 128.2, 128.3, 128.4, 128.6, 129.6, 140.1,
3.6.3. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-
1
hexanoate 12c.26b Oil, yieldZ63%. H NMR d: 0.72 (t,
3H, JZ6.9 Hz, H-6), 1.18 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.11–1.29 (m, 10H, H-4, H-5), 1.24 (d, 3H, JZ6.4 Hz,

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C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
CH(Ph)CH3), 1.46 (s, 1H, NH), 2.27 (dd, 1H, JZ5.4,
14.6 Hz, H-2), 2.37 (dd, 1H, JZ5.6, 14.6 Hz, H-2), 2.67–
2.78 (m, 1H, H-3), 3.81 (q, 1H, JZ6.4 Hz, CH(Ph)CH3),
4.06 (q, 2H, JZ7.2 Hz, OCH2CH3), 7.18–7.25 (m, 5H, Ph).
13C NMR d: 14.2 (C-6), 14.4 (OCH2CH3), 19.3 (C-5), 25.1
(CH(Ph)CH3), 37.8 (C-4), 38.8 (C-2), 52.0 (C-3), 55.2
(CH(Ph)CH3), 60.3 (OCH2CH3), 126.9, 127.0, 128.1, 146.2
(Ph), 172.7 (C-1). [a]2D5 C28.9 (c 1.0, CHCl3).
Water (30 mL) and ether (15 mL) were added. The aqueous
phase was separated and extracted with ether (2!30 mL).
The combined organic phases were dried over MgSO4 and
concentrated. The crude product was purified by silica gel
chromatography (cyclohexane/ether: 90:10).
3.7.1. Ethyl 3-((R)-1-phenylethylamino)-2-(phenyl-
selanyl)butanoate 9a, 900a. Oil, 9a/900a: 50/50, yieldZ65%.
3.6.4. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-4-
methylpentanoate 12d.26 Oil, yieldZ53%. 1H NMR d:
0.79 (d, 3H, JZ6.6 Hz, H-5), 0.87 (d, 3H, JZ6.9 Hz, H-5),
1.26 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.31 (d, 3H, JZ6.6 Hz,
CH(Ph)CH3), 1.44 (s, 1H, NH), 1.62–1.75 (m, 1H, H-4),
2.32 (dd, 1H, JZ6.4, 14.6 Hz, H-2), 2.43 (dd, 1H, JZ5.4,
14.6 Hz, H-2), 2.61–2.67 (m, 1H, H-3), 3.84 (q, 1H, JZ
6.6 Hz, CH(Ph)CH3), 4.13 (q, 2H, JZ7.2 Hz, OCH2CH3),
7.21–7.35 (m, 5H, Ph). 13C NMR d: 14.4 (OCH2CH3), 18.5
(C-5), 18.8 (C-5), 24.9 (CH(Ph)CH3), 31.5 (C-4), 36.2 (C-
2), 55.6 (CH(Ph)CH3), 57.8 (C-3), 60.3 (OCH2CH3), 126.9,
127.0, 128.4, 146.4 (Ph), 173.2 (C-1). [a]2D5 C25.4 (c 1.0,
CHCl3).
3.7.1.1. (2S,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
(phenylselanyl)butanoate 9a. (Second eluted). 1H NMR d:
1.10 (d, 3H, JZ6.4 Hz, H-4), 1.15 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.31 (d, 3H, JZ6.6 Hz, CH(Ph)CH3), 1.70 (s,
1H, NH), 3.11 (quint, 1H, JZ6.4 Hz, H-3), 3.83 (d, 1H, JZ
6.4 Hz, H-2), 3.86 (q, 1H, JZ6.6 Hz, CH(Ph)CH3), 4.04–
4.10 (m, 2H, OCH2CH3), 7.26–7.55 (m, 10H, Ph). 13C NMR
d: 14.2 (OCH2CH3), 19.3 (C-4), 24.5 (CH(Ph)CH3), 51.4,
52.7 (C-2, C-3), 55.7 (CH(Ph)CH3), 61.1 (OCH2CH3),
126.7, 126.9, 128.2, 128.5, 129.1, 129.3, 135.2, 146.3 (Ph),
172.1 (C-1). [a]2D5 K18.5 (c 1.0 in CHCl3).
3.7.1.2. (2R,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
1
(phenylselanyl)butanoate 900a. (First eluted). H NMR d:
3.6.5. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-4-
1.13 (d, 3H, JZ6.4 Hz, H-4), 1.16 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.22 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.64 (s,
1H, NH), 3.13 (quint, 1H, JZ6.4 Hz, H-3), 3.73 (d, 1H, JZ
6.4 Hz, H-2), 3.77 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.9 (q,
2H, JZ7.2 Hz, OCH2CH3), 7.24–7.62 (m, 10H, Ph). 13C
NMR d: 14.2 (OCH2CH3), 19.4 (C-4), 24.0 (CH(Ph)CH3),
52.5, 52.6 (C-2, C-3), 55.8 (CH(Ph)CH3), 61.0 (OCH2CH3),
126.7, 127.0, 128.1, 128.5, 129.2, 129.7, 134.8, 146.4 (Ph),
172.8 (C-1). [a]2D5 K33.4 (c 1.0 in CHCl3).
1
phenylbutanoate 12e. Oil, yieldZ62%. H NMR d: 1.18
(t, 3H, JZ7.2 Hz, OCH2CH3), 1.20 (d, 3H, JZ6.6 Hz,
CH(Ph)CH3), 1.52 (s, 1H, NH), 2.32 (d, 2H, JZ6.1 Hz, H-
4), 2.58 (dd, 1H, JZ7.4, 13.6 Hz, H-2), 2.66 (dd, 1H, JZ
6.4, 13.6 Hz, H-2), 2.92–3.02 (m, 1H, H-3), 3.78 (q, 1H, JZ
6.6 Hz, CH(Ph)CH3), 4.06 (q, 2H, JZ7.2 Hz, OCH2CH3),
6.97–7.19 (m, 10H, Ph). 13C NMR d: 14.4 (OCH2CH3), 24.8
(CH(Ph)CH3), 38.7 (C-4), 41.6 (C-2), 53.7 (C-3), 55.3
(CH(Ph)CH3), 60.4 (OCH2CH3), 126.4, 126.6, 126.9, 128.3,
128.4, 129.5, 138.9, 145.7 (Ph), 172.4 (C-1). Anal. Calcd for
C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found: C, 77.36; H,
9.41; N, 4.74. [a]2D5 C26.3 (c 1.0, CHCl3).
3.7.2. Ethyl 3-((R)-1-phenylethylamino)-2-(phenyl-
selanyl)pentanoate 9b, 900b. Oil, 9b/900b: 50/50, yieldZ59%.
3.7.2.1. (2S,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
(phenylselanyl)pentanoate 9b. (Second eluted). H NMR
3.6.6. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-3-
1
1
phenylpropanoate 12g.26 Oil, yieldZ48%. H NMR d:
d: 0.84 (t, 3H, JZ7.2 Hz, H-5), 1.19 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.34 (d, 3H, JZ6.6 Hz, CH(Ph)CH3), 1.66–
1.80 (m, 3H, H-4, NH), 2.32–2.41 (m, 1H, H-3), 3.87 (q, 1H,
JZ6.6 Hz, CH(Ph)CH3), 4.01 (d, 1H, JZ5.4 Hz, H-2),
1.10 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.26 (d, 3H, JZ6.4 Hz,
CHaCH3), 1.77 (s, 1H, NH), 2.56 (dd, 1H, JZ6.1, 15.1 Hz,
H-2), 2.64 (dd, 1H, JZ7.7, 15.1 Hz, H-2), 3.58 (q, 1H, JZ
6.4 Hz, CH(Ph)CH3), 3.99 (q, 2H, JZ7.2 Hz, OCH2CH3),
4.12 (dd, 1H, JZ6.1, 7.7 Hz, H-3), 7.16–7.21 (m, 10H, Ph).
13C NMR d: 14.3 (OCH2CH3), 22.4 (CH(Ph)CH3), 43.0 (C-2),
54.7 (CH(Ph)CH3), 57.0 (C-3), 60.6 (OCH2CH3), 126.7,
126.9, 127.0, 127.1, 128.5, 128.7, 142.9, 146.1 (Ph), 171.9
(C-1). Anal. Calcd for C19H21NO2: C, 76.75; H, 7.80; N, 4.71.
Found: C, 76.95; H, 8.13; N, 5.02. [a]2D5 C21.7(c 1.0, CHCl3).
4.04–4.19 (m, 2H, OCH2CH3), 7.19–7.60 (m, 10H, Ph). 13
C
NMR d: 10.5 (C-5), 14.2 (OCH2CH3), 24.7 (CHaCH3), 25.2
(C-4), 49.9 (C-2), 55.5 (CH(Ph)CH3), 58.4 (C-3), 61.2
(OCH2CH3), 126.8, 128.1, 128.4, 128.6, 129.1, 129.2,
135.2, 146.1 (Ph), 172.2 (C-1). [a]2D5 K17.9 (c 1.0, CHCl3).
3.7.2.2. (2R,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
(phenylselanyl)pentanoate 900b. (First eluted). 1H NMR d:
0.73 (t, 3H, JZ7.2 Hz, H-5), 1.16 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.21 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.39–
1.58 (m, 2H, H-4), 1.73 (s, 1H, NH), 2.85–3.91 (m, 1H, H-3),
3.74 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 3.81 (d, 1H, JZ5.9 Hz,
H2), 3.96–4.13 (m, 2H, OCH2CH3), 7.22–7.70 (m, 10H, Ph).
13C NMR d: 10.1 (C-5), 14.1 (OCH2CH3), 24.0(CH(Ph)CH3),
25.4 (C-4), 50.2 (C-2), 55.6 (CH(Ph)CH3), 57.8 (C-3), 61.0
(OCH2CH3), 126.8, 127.0, 128.0, 128.4, 129.3, 129.4, 134.7,
146.3 (Ph), 172.9 (C1). [a]2D5 K30.7 (c 1.0, CHCl3).
3.7. Synthesis of a-(phenylselanyl)b-aminoesters 9, 900
n-Butyllithium 2.5 M in hexane (1.26 mL, 3.15 mmol,
2.1 equiv) was added dropwise to a solution of diisopropyl-
amine (318 mg, 3.15 mmol, 2.1 equiv) in THF (20 mL) at
0 8C, under argon. After 15 min of stirring at 0 8C, the
mixture was cooled to K78 8C and a solution of the
b-aminoester 12 (1.5 mmol, 1 equiv) in THF (2 mL) was
slowly introduced. After 20 min at K78 8C, a solution of
PhSeBr (460 mg, 1.95 mmol, 1.3 equiv) in THF (2 mL) was
added. After 20 min of stirring at K78 8C the mixture was
quenched with a saturated aqueous solution of ammonium
chloride (5 mL) and allowed to reach the room temperature.
3.7.3. Ethyl 3-((R)-1-phenylethylamino)-2-(phenyl-
selanyl)hexanoate 9c, 900c. Oil, 9c/900c: 50/50, yieldZ56%.

C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
2667
3.7.3.1. (2S,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
(phenylselanyl)hexanoate 9c. (Second eluted). 1H NMR d:
0.67 (t, 3H, JZ7.2 Hz, H-6), 1.10 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.21 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.15–
1.29 (m, 2H, H-5), 1.48–1.42 (m, 2H, H-4), 1.68 (s, 1H,
NH), 2.75–2.79 (m, 1H, H-3), 3.75 (q, 1H, JZ6.4 Hz,
CH(Ph)CH3), 3.93 (d, 1H, JZ4.8 Hz, H-2), 4.03 (dq, 1H,
JZ7.2, 10.7 Hz, OCH2CH3), 4.06 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 7.16–7.45 (m, 10H, Ph). 13C NMR d: 14.0, 14.2
(C-6, OCH2CH3), 19.4 (C-5), 24.8 (CH(Ph)CH3), 34.7
(C-4), 50.0 (C-2), 55.4 (CH(Ph)CH3), 56.7 (C-3), 61.2
(OCH2CH3), 126.9, 127.5, 127.9, 128.2, 128.6, 129.2,
135.4, 146.0 (Ph), 172.1 (C-1). [a]2D5 K17.4 (c 1.0 in
CHCl3).
3.7.5. Ethyl 4-phenyl-3-((R)-1-phenylethylamino)-2-
(phenylselanyl)butanoate 9e, 900e. Oil, 9e/900e: 70/30,
yieldZ61%.
3.7.5.1. (2S,3R)-Ethyl 4-phenyl-3-((R)-1-phenylethyl-
amino)-2-(phenylselanyl)butanoate 9e. (Second eluted).
1H NMR d: 1.06 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.19 (d, 3H,
JZ6.6 Hz, CH(Ph)CH3), 1.67 (s, 1H, NH), 2.61 (dd, 1H,
JZ7.9, 13.7 Hz, H-4), 2.94 (dd, 1H, JZ5.1, 13.7 Hz, H-4),
3.09–3.15 (m, 1H, H-3), 3.78 (q, 1H, JZ6.6 Hz,
CH(Ph)CH3), 3.85 (d, 1H, JZ4.9 Hz, H-2), 3.95 (dq, 1H,
JZ7.2, 10.7 Hz, OCH2CH3), 3.97 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 6.84–7.07 (m, 15H, Ph). 13C NMR d: 14.2
(OCH2CH3), 24.6 (CH(Ph)CH3), 38.9 (C-4), 49.6 (C-2), 55.6
(CH(Ph)CH3), 58.5 (C-3), 61.1 (OCH2CH3), 126.4, 126.6,
126.8, 128.1, 128.3, 128.4, 128.5, 129.1, 129.7, 135.0, 138.7,
145.6 (Ph), 172.3 (C-1). [a]2D5 K29.6 (c 1.0 in CHCl3).
3.7.3.2. (2R,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
1
(phenylselanyl)hexanoate 900c. (First eluted). H NMR d:
0.76 (t, 3H, JZ7.2 Hz, H-6), 1.15 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.22 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.16–
1.34 (m, 2H, H-5), 1.43–1.49 (m, 2H, H-4), 1.68 (s, 1H,
NH), 2.95–3.01 (m, 1H, H-3), 3.79 (q, 1H, JZ6.4 Hz,
CH(Ph)CH3), 3.90 (d, 1H, JZ5.4 Hz, H-2), 4.01 (q, 2H, JZ
7.2 Hz, OCH2CH3), 7.27–7.63 (m, 10H, Ph). 13C NMR d:
14.2, 14.3 (C-6, OCH2CH3), 19.1 (C-5), 24.2 (CH(Ph)CH3),
35.3 (C-4), 51.0 (C-2), 55.6 (CH(Ph)CH3), 56.4 (C-3), 61.1
(OCH2CH3), 127.0, 127.1, 128.1, 128.5, 129.2, 129.5,
134.8, 146.7 (Ph), 172.9 (C-1). [a]2D5 K29.8 (c 1.0 in
CHCl3).
3.7.5.2. (2R,3R)-Ethyl 3-((R)-1-phenylethylamino)-2-
1
(phenylselanyl)butanoate 900e. (First eluted). H NMR d:
1.10 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.16 (d, 3H, JZ6.4 Hz,
CH(Ph)CH3), 1.87 (s, 1H, NH), 2.75 (d, 2H, JZ6.6 Hz,
H-4), 3.19 (td, 1H, JZ5.4, 6.6 Hz, H-3), 3.66 (d, 1H, JZ
5.4 Hz, H-2), 3.74 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.04
(q, 2H, JZ7.2 Hz, OCH2CH3), 6.94–7.48 (m, 15H, Ph). 13
C
NMR d: 14.2 (OCH2CH3), 23.9 (CH(Ph)CH3), 39.2 (C-4),
49.6 (C-2), 55.9 (CH(Ph)CH3), 58.3 (C-3), 61.0
(OCH2CH3), 126.4, 126.7, 126.9, 128.0, 128.4, 128.5,
129.1, 129.5, 129.9, 134.6, 138.5, 146.0 (Ph), 172.8 (C-1).
[a]2D5 K16.3 (c 1.0 in CHCl3).
3.7.4. Ethyl 3-((R)-1-phenylethylamino)-4-methyl-2-
(phenylselanyl)pentanoate 9d, 900d. Oil, 9d/900d: 60/40,
yieldZ58%.
3.7.6. Ethyl 3-phenyl-3-((R)-1-phenylethylamino)-2-
(phenylselanyl)propanoate 9g, 900g. Oil, 9g/900g: 50/50,
yieldZ57%.
3.7.4.1. (2S,3R)-Ethyl 3-((R)-1-phenylethylamino)-4-
methyl-2-(phenylselanyl)pentanoate 9d. (First eluted). 1H
NMR d: 0.78 (d, 3H, JZ6.9 Hz, H-5), 0.81 (d, 3H, JZ
6.9 Hz, H-5), 1.04 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.38 (d,
3H, JZ6.6 Hz, CH(Ph)CH3), 1.55 (s, 1H, NH), 1.83 (septd,
1H, JZ3.8, 6.9 Hz, H-4), 2.95 (dd, 1H, JZ3.8, 6.9 Hz,
H-3), 3.89 (q, 1H, JZ6.6 Hz, CH(Ph)CH3), 3.91 (dq, 1H,
JZ7.2, 10.4 Hz, OCH2CH3), 3.95 (dq, 1H, JZ7.2, 10.4 Hz,
OCH2CH3), 4.05 (d, 1H, JZ6.9 Hz, H-2), 7.26–7.62 (m,
10H, Ph). 13C NMR d: 14.0 (OCH2CH3), 17.9 (C-5), 19.9
(C-5), 24.1 (CH(Ph)CH3), 31.6 (C-4), 51.1 (C-2), 56.8
(CH(Ph)CH3), 59.8 (C-3), 61.1 (OCH2CH3), 127.0, 127.1,
128.1, 128.4, 129.0, 130.0, 135.6, 146.2 (Ph), 172.8 (C-1).
[a]2D5 K19.6 (c 1.0 in CHCl3).
3.7.6.1. (2S,3R)-Ethyl 3-phenyl-3-((R)-1-phenylethyl-
amino)-2-(phenylselanyl)propanoate 9g. (First eluted). 1H
NMR d: 0.86 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.34 (d, 3H,
JZ6.6 Hz, CH(Ph)CH3), 2.17 (s, 1H, NH), 3.56 (q, 1H, JZ
6.6 Hz, CH(Ph)CH3), 3.73 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 3.75 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
3.98 (d, 1H, JZ9.7 Hz, H-2), 4.25 (d, 1H, JZ9.7 Hz, H-3),
7.24–7.62 (m, 15H, Ph). 13C NMR d: 13.8 (OCH2CH3), 21.8
(CH(Ph)CH3), 52.7 (C-2), 54.6 (CH(Ph)CH3), 60.8
(OCH2CH3), 60.9 (C-3), 126.7, 126.8, 127.6, 127.8, 128.1,
128.3, 128.4, 128.5, 129.0, 135.9, 140.5, 146.1 (Ph), 171.1
(C-1). [a]2D5 K15.7 (c 1.0 in CHCl3).
3.7.4.2. (2R,3R)-Ethyl 3-((R)-1-phenylethylamino)-4-
methyl-2-(phenylselanyl)pentanoate 900d. (Second
1
eluted). H NMR d: 0.68 (d, 3H, JZ6.9 Hz, H-5), 0.79 (d,
3.7.6.2. (2R,3R)-Ethyl 3-phenyl-3-((R)-1-phenylethyl-
amino)-2-(phenylselanyl)propanoate 900g. (Second
3H, JZ6.9 Hz, H-5), 1.16 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.28 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.65 (s, 1H, NH), 2.01
(septd, 1H, JZ4.3, 6.9 Hz, H-4), 2.96 (dd, 1H, JZ4.3,
6.9 Hz-3), 3.82 (d, 1H, JZ6.9 Hz, H-2), 3.92 (q, 1H, JZ
6.4 Hz, CH(Ph)CH3), 4.06 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 4.09 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
7.28–7.63 (m, 10H, Ph). 13C NMR d: 14.1 (OCH2CH3), 17.6
(C-5), 20.1 (C-5), 24.2 (CHaCH3), 31.4 (C-4), 49.9 (C-2),
56.7 (CH(Ph)CH3), 61.0 (OCH2CH3), 61.7 (C-3), 127.2,
127.3, 128.3, 128.6, 129.2, 130.0, 135.8, 146.4 (Ph), 173.3
(C-1). [a]2D5 K33.5 (c 1.0 in CHCl3).
1
eluted). H NMR d: 1.10 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.28 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 2.35 (s, 1H, NH), 3.61
(q, 1H, JZ6.4 Hz, CH(Ph)CH3), 3.89 (d, 1H, JZ8.6 Hz,
H-2), 4.03 (q, 2H, JZ7.2 Hz, OCH2CH3), 4.31 (d, 1H, JZ
8.6 Hz, H-3), 7.18–7.25 (m, 15H, Ph). 13C NMR d: 14.1
(OCH2CH3), 22.1 (CH(Ph)CH3), 51.7 (C-2), 55.1
(CH(Ph)CH3), 61.0 (OCH2CH3), 62.0 (C-3), 126.7, 126.8,
127.1, 127.6, 127.7, 128.1, 128.4, 128.5, 128.9, 135.2, 140.4,
146.3 (Ph), 172.2 (C-1). [a]2D5 K23.8 (c 1.0 in CHCl3).

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C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
3.8. Cyclisation of a-(phenylselanyl)b-aminoesters 9, 900
3.8.6. (2S,3R)-Ethyl 1-((R)-1-phenylethyl)-3-propyl-
aziridine-2-carboxylate 600c. Oil, yieldZ50% (A),
yieldZ51% (B). 1H NMR d: 0.69 (t, 3H, JZ7.2 Hz,
CH2CH2CH3), 0.98–1.07 (m, 2H, CH2CH2CH3), 1.24–1.41
(m, 2H, CH2CH2CH3), 1.30 (d, 3H, JZ6.4 Hz,
CH(Ph)CH3), 1.34 (t, 3H, JZ7.2 Hz, OCH2CH3), 2.15–
2.23 (m, 1H, H-3), 2.53 (d, 1H, JZ2.8 Hz, H-2), 3.80 (q,
1H, JZ6.4 Hz, CH(Ph)CH3), 4.23 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 4.25 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
7.25–7.41 (m, 5H, Ph). 13C NMR d: 13.7 (CH3CH2CH2),
14.4 (OCH2CH3), 20.1 (CH3CH2CH2), 22.8 (CH(Ph)CH3),
34.8 (CH3CH2CH2), 41.1 (C-2), 46.7 (C-3), 59.5
(CH(Ph)CH3), 61.2 (OCH2CH3), 127.3, 127.5, 128.4,
144.7 (Ph), 170.0 (C]O). MS m/z: 261 (MC, 1), 156
(91), 105 (100), 82 (69). IR nmax (neat) cmK1: 2968, 1728,
1455, 1189. Anal. Calcd for C16H23NO2: C, 73.53; H, 8.87;
N, 5.36. Found: C, 73.75; H, 9.01; N, 5.48. [a]2D5 C17.3 (c
1.0 in CH2Cl2).
The protocols are the same as for the cyclisation of b-
(phenylselanyl)a-aminoesters 2.
Procedure A with Me3OBF4. a-(Phenylselanyl)b-amino-
esters 9 (or 900) afforded aziridines 6 (or 600).
Procedure B with NBS. a-(Phenylselanyl)b-aminoesters 9
(or 900) afforded aziridines 6 (or 600), except for 9a and 9f,
which lead, respectively, to 600a and 600f.
3.8.1. (2R,3R)-Ethyl 3-methyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 6a.5b YieldZ51% (A).
3.8.2. (2S,3R)-Ethyl 3-methyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 600a. Oil, two invertomers: 60/40,
1
yieldZ53% (A), yieldZ59% (B). Major: H NMR d: 1.04
(d, 3H, JZ5.4 Hz, CH3), 1.18 (d, 3H, JZ6.6 Hz,
CH(Ph)CH3), 1.26 (t, 3H, JZ7.2 Hz, OCH2CH3), 2.12–
2.20 (m, 1H, H-3), 2.44 (d, 1H, JZ2.8 Hz, H-2), 3.77 (q,
1H, JZ6.6 Hz, CH(Ph)CH3), 4.16 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 4.19 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
7.23–7.32 (m, 5H, Ph). 13C NMR d: 14.5 (OCH2CH3), 18.0
(CH3), 23.5 (CH(Ph)CH3), 41.7 (C-2), 42.1 (C-3), 59.1
(Ca), 61.3 (OCH2CH3), 127.4, 128.7, 128.8, 145.3 (Ph),
170.0 (C]O). Minor: dH (300 MHz, CDCl3): 1.14 (d, 3H,
JZ7.2 Hz, OCH2CH3), 1.36 (d, 3H, JZ6.4 Hz, CHaCH3),
1.40 (t, 3H, JZ6.1 Hz, CH3), 1.77 (d, 1H, JZ2.8 Hz, H-2),
2.56–2.65 (m, 1H, H-3), 3.27 (q, 1H, JZ6.4 Hz,
CH(Ph)CH3), 4.05 (q, 2H, JZ7.2 Hz, OCH2CH3), 7.23–
7.32 (m, 5H, Ph). 13C NMR d: 10.9 (CH3), 14.6
(OCH2CH3), 24.9 (CH(Ph)CH3), 41.4 (C-3), 43.7 (C-2),
60.4 (CH(Ph)CH3), 61.2 (OCH2CH3), 127.0, 128.7, 128.8,
145.3 (Ph), 170.2 (C]O). MS m/z: 233 (MC, 2), 128 (77),
105 (100). IR nmax (neat) cmK1: 2979, 1728, 1449, 1190.
Anal. Calcd for C14H19NO2: C, 72.10; H, 8.21; N, 6.00.
Found: C, 71.87; H, 8.23; N, 5.89. [a]2D5 C34.1 (c 1.0 in
CH2Cl2).
3.8.7. (2R,3R)-Ethyl 1-((R)-1-phenylethyl)-3-iso-propyl-
aziridine-2-carboxylate 6d. Oil, yieldZ44% (A), yieldZ
49% (B). H NMR d: 0.42 (d, 3H, JZ6.4 Hz, CH(CH3)2),
1
0.67 (d, 3H, JZ6.4 Hz, CH(CH3)2), 1.22 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.38–1.40 (m, 4H, CH(CH3)2, CH(Ph)CH3),
1.41–1.48 (m, 1H, H-3), 2.15 (d, 1H, JZ6.4 Hz, H-2), 2.45
(q, 1H, JZ6.6 Hz, CH(Ph)CH3), 4.15 (q, 2H, JZ7.2 Hz,
OCH2CH3), 7.19–7.33 (m, 5H, Ph). 13C NMR d: 14.4
(OCH2CH3), 19.8 (CH(CH3)2), 20.6 (CH(CH3)2), 22.1
(CH(Ph)CH3), 27.2 (CH(CH3)2), 43.2 (C-2), 53.2 (C-3),
59.9 (OCH2CH3), 70.4 (CH(Ph)CH3), 127.6, 127.8, 128.4,
143.4 (Ph), 170.2 (C]O). MS m/z: 261 (MC, 3), 218 (11),
156 (100), 105 (74), 82 (85). IR nmax (neat) cmK1: 2978,
1744, 1453, 1184. Anal. Calcd for C16H23NO2: C, 73.53; H,
8.87; N, 5.36. Found: C, 73.87; H, 9.03; N, 5.16. [a]D25
C48.5 (c 1.0 in CH2Cl2).
3.8.8. (2S,3R)-Ethyl 1-((R)-1-phenylethyl)-3-iso-propyl-
aziridine-2-carboxylate 600d. Oil, yieldZ48% (A), yieldZ
1
53% (B). H NMR d: 0.37 (d, 3H, JZ6.6 Hz, CH(CH3)2),
0.71 (d, 3H, JZ6.6 Hz, CH(CH3)2), 1.18–1.20 (m, 1H,
CH(CH3)2), 1.21 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.27 (t,
3H, JZ7.2 Hz, OCH2CH3), 1.92 (dd, 1H, JZ2.8, 7.7 Hz,
H-3), 2.47 (d, 1H, JZ2.8 Hz, H-2), 3.69 (q, 1H, JZ6.4 Hz,
CH(Ph)CH3), 4.12–4.23 (m, 2H, OCH2CH3), 7.18–7.32 (m,
5H, Ph). 13C NMR d: 14.4 (OCH2CH3), 19.5 (CH(CH3)2),
19.6 (CH(CH3)2), 22.3 (CH(Ph)CH3), 31.2 (CH(CH3)2),
39.9 (C-2), 53.5 (C-3), 59.9 (CH(Ph)CH3), 61.2
(OCH2CH3), 127.9, 128.4, 128.6, 144.6 (Ph), 170.1
(C]O). MS m/z: 261 (MC, 3), 156 (60), 105 (83), 82
(100). IR nmax (neat) cmK1: 2968, 1723, 1449, 1190. Anal.
Calcd for C16H23NO2: C, 73.53; H, 8.87; N, 5.36. Found: C,
73.53; H, 8.94; N, 5.28. [a]2D5 K22.8 (c 1.0 in CH2Cl2).
3.8.3. (2R,3R)-Ethyl 1-((R)-1-phenylethyl)-3-ethyl-
aziridine-2-carboxylate 6b. YieldZ53% (A).
3.8.4. (2S,3R)-Ethyl 1-((R)-1-phenylethyl)-3-ethyl-
aziridine-2-carboxylate 600b. Oil, yieldZ47% (A),
yieldZ51% (B). 1H NMR d: 0.62 (t, 3H, JZ7.4 Hz,
CH2CH3), 1.30 (d, 3H, JZ6.6 Hz, CH(Ph)CH3), 1.37 (t, 3H,
JZ7.2 Hz, OCH2CH3), 1.17–1.52 (m, 2H, CH2CH3), 2.17
(ddd, 1H, JZ2.8, 5.4, 6.7 Hz, H-3), 2.56 (d, 1H, JZ2.8 Hz,
H-2), 3.83 (q, 1H, JZ6.6 Hz, CH(Ph)CH3), 4.12–4.22 (m,
2H, OCH2CH3), 7.22–7.49 (m, 5H, Ph). 13C NMR d: 11.0
(CH2CH3), 14.4 (OCH2CH3), 22.8 (CH(Ph)CH3), 25.7
(CH2CH3), 40.7 (C-2), 48.2 (C-3), 59.4 (CH(Ph)CH3),
61.2 (OCH2CH3), 127.3, 127.4, 128.4, 144.7 (Ph), 170.0
(C]O). MS m/z: 247 (MC, 14), 142 (34), 105 (100). IR
nmax (neat) cmK1: 2970, 1728, 1450, 1190. Anal. Calcd for
C15H21NO2: C, 58.29; H, 8.50; N, 5.66. Found: C, 58.85; H,
8.67; N, 5.31. [a]2D5 C22.6 (c 1.0, CH2Cl2).
3.8.9. (2R,3R)-Ethyl 3-benzyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 6e.5b YieldZ42% (A), yieldZ
53% (B).
3.8.10. (2S,3R)-Ethyl 3-benzyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 600e. Oil, yieldZ39% (A),
yieldZ48% (B). 1H NMR d: 1.19 (d, 3H, JZ6.4 Hz,
CH(Ph)CH3), 1.25 (t, 3H, JZ6.9 Hz, OCH2CH3), 2.39 (td,
1H, JZ2.8, 5.9 Hz, H-3), 2.53 (dd, 1H, JZ5.9, 14.6 Hz,
CH2Ph), 2.58 (d, 1H, JZ2.8 Hz, H-2), 2.62 (dd, 1H, JZ5.9,
3.8.5. (2R,3R)-Ethyl 1-((R)-1-phenylethyl)-3-propyl-
aziridine-2-carboxylate 6c. YieldZ47% (A), yieldZ
61% (B).

C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
2669
10041. (e) Chuang, T.-H.; Sharpless, K. B. Org. Lett. 2000, 2,
3555. (f) Wu, J.; Hou, X.-L.; Dai, L.-X. J. Chem. Soc., Perkin
Trans. 1 2001, 1314. Hou, X.-L.; Fan, R. H.; Dai, L.-X. J. Org.
Chem. 2002, 67, 5295. (g) Caiazzo, A.; Dalili, S.; Yudin, A. K.
14.6 Hz, CH2Ph), 3.75 (q, 1H, JZ6.4 Hz, CH(Ph)CH3),
4.12 (dq, 1H, JZ6.9, 10.5 Hz, OCH2CH3), 4.16 (dq, 1H,
JZ6.9, 10.5 Hz, OCH2CH3), 6.86–7.31 (m, 10H, Ph). 13C
NMR d: 14.4 (OCH2CH3), 23.0 (CH(Ph)CH3), 38.8
(CH2Ph), 40.6 (C-2), 47.3 (C-3), 59.4 (CH(Ph)CH3), 61.3
(OCH2CH3), 126.2, 126.6, 127.2, 127.3, 128.4, 128.6,
´
Org. Lett. 2002, 4, 2597. (h) Prevost, N.; Shipman, M.
Tetrahedron 2002, 58, 7165. (i) Sugihara, Y.; Iimura, S.;
Nakayama, J. J. Chem. Soc. 2002, 134. (l) Davoli, P.; Moretti, I.;
Prati, F.; Apler, H. J. Org. Chem. 1999, 64, 518.
138.2, 144.4 (Ph), 169.7 (C]O). IR nmax (neat) cmK1
:
2978, 1723, 1449, 1190. Anal. Calcd for C20H23NO2: C,
77.60; H, 7.49; N, 4.53. Found: C, 77.88; H, 7.76; N, 4.69.
[a]2D5 C13.8 (c 1.0 in CH2Cl2).
5. (a) Cardillo, G.; Gentilucci, L.; Tolomelli, A. Aldrichim. Acta
2003, 36, 39. (b) Lee, K.-D.; Suh, J.-M.; Park, J.-H.; Ha, H.-J.;
Choi, H. G.; Park, C. S.; Chang, J. W.; Lee, W. K.; Dong, Y.;
Yun, H. Tetrahedron 2001, 57, 8267.
3.8.11. (2R,3R)-Ethyl 3-phenyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 6g.5b Oil, yieldZ49% (A).
6. (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599. (b)
Osborn, H. M. I.; Sweeney, J. Tetrahedron: Asymmetry 1997,
8, 1693. (c) Atkinson, R. S. Tetrahedron 1999, 55, 1519.
7. (a) Atkinson, R. S. Tetrahedron 1999, 55, 1519. Atkinson,
R. S.; Ayscough, A. P.; Gattrell, W. T.; Raynham, T. M.
J. Chem. Soc., Perkin Trans. 1 1998, 2783. Atkinson, R. S.;
Meades, C. K. J. Chem. Soc., Perkin Trans. 1 2001, 1, 1518.
Atkinson, R. S.; Draycott, R. D.; Hirst, D. J.; Parratt, M. J.;
Raynham, T. M. Tetrahedron Lett. 2002, 43, 2083. (b) Evans,
D. A.; Fault, M. M.; Bilodeau, M. T.; Anderson, B. A.; Barnes,
D. M. J. Am. Chem. Soc. 1993, 115, 5328. (c) Li, Z.; Quan,
R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889.
(d) Gillespie, K. M.; Sanders, C. J.; O’Shaughnessy, P.;
Westmoreland, I.; Thickitt, C. P.; Scott, P. J. Org. Chem. 2002,
67, 3450. (e) Quan, R. W.; Li, Z.; Jacobsen, E. N. J. Am. Chem.
Soc. 1996, 118, 8156. (f) Cardillo, G.; Gentilucci, L.;
Tomasini, C.; Visa Castejon-Bordas, M. P. Tetrahedron:
Asymmetry 1996, 7, 755. Cardillo, G.; Fabbroni, S.; Gentilucci,
L.; Gianotti, M.; Perciaccante, R.; Tolomelli, A. Tetrahedron:
Asymmetry 2002, 13, 1407.
3.8.12. (2S,3R)-Ethyl 3-phenyl-1-((R)-1-phenylethyl)-
aziridine-2-carboxylate 600g. Oil, yieldZ52% (A),
yieldZ55% (B). 1H NMR d: 1.22–1.31 (m, 6H,
CH(Ph)CH3, OCH2CH3), 2.75 (d, 1H, JZ2.8 Hz, H-2),
3.15 (d, 1H, JZ2.8 Hz, H-3), 4.01 (q, 1H, JZ6.4 Hz,
CH(Ph)CH3), 4.15 (m, 2H, OCH2CH3), 7.12–7.32 (m, 10H,
Ph). 13C NMR d: 14.2 (OCH2CH3), 23.5 (CH(Ph)CH3), 44.6
(C-2), 47.9 (C-3), 60.6 (CH(Ph)CH3), 61.2 (OCH2CH3),
126.9, 127.3, 127.8, 128.0, 128.5, 129.1, 135.7, 144.5 (Ph),
167.9 (C]O). M.S. m/z: 295 (MC, 1), 190 (100), 117 (79),
105 (47). IR nmax (neat) cmK1: 2977, 1724, 1455, 1184.
Anal. Calcd for C19H21NO2: C, 77.03; H, 7.17; N, 4.74.
Found: C, 77.17; H, 7.35; N, 4.93. [a]2D5 C22 (c 1.0 in
CH2Cl2).
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